Methods and apparatus for reducing sweat production

ABSTRACT

Methods and apparatuses are provided for reducing sweat production via, for example, the removal, disablement, and incapacitation of sweat glands in the epidermis, dermis and subdermal tissue regions of a patient. In one embodiment, a method of treating a patient is provided which involves identifying a patient having a condition of excessive sweating, positioning an energy delivery device proximate to a skin tissue of the patient and delivering energy to sweat glands to halt secretion of sweat. The energy delivery device may include microwave delivery devices, RF delivery devices, and cryogenic therapy devices. Some embodiments may include using a cooling element for avoiding destruction of non-target tissue and/or a suction device to localize treatment at specific portions of the skin fold.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.12/450,859, filed Oct. 16, 2009, which is a national phase ofInternational Application No. PCT/US2008/060935, filed Apr. 18, 2008;which application claims benefit of the following U.S. ProvisionalApplications: Application No. 60/912,899, entitled “Methods andApparatus for Reducing Sweat Production,” filed Apr. 19, 2007,Application No. 61/013,274, entitled “Methods, Delivery and Systems forNon-Invasive Delivery of Microwave Therapy,” filed Dec. 12, 2007, andApplication No. 61/045,937, entitled “Systems and Methods for Creatingan Effect Using Microwave Energy in Specified Tissue,” filed Apr. 17,2008. The entire disclosures of all of the priority applications arehereby expressly incorporated by reference in their entirety.

BACKGROUND

1. Field of the Invention

The present application relates to methods and apparatuses for reducingsweat production. In particular, the present application relates tomethods and apparatuses for reducing sweat production via the removal,disablement, incapacitation of apocrine and eccrine glands in the dermaland subcutaneous tissue.

2. Description of the Related Art

It is known that energy-based therapies can be applied to tissuethroughout the body to achieve numerous therapeutic and/or aestheticresults. There remains a continual need to improve on the effectivenessof these energy-based therapies and provide beneficial pathologicalchange with minimal adverse side effects or discomfort.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features, aspects and advantages of the various devices,systems and methods presented herein are described with reference todrawings of certain embodiments, which are intended to illustrate, butnot to limit, such devices, systems, and methods. It is to be understoodthat the attached drawings are for the purpose of illustrating conceptsof the embodiments discussed herein and may not be to scale.

FIG. 1 shows a cross-sectional view of the skin, its internal structuresand surrounding tissue.

FIG. 2 shows a cross-sectional view of a target tissue having a zone ofthermal treatment according to one embodiment.

FIGS. 3A and 3B show a device having an energy applicator according toone embodiment.

FIG. 4 shows an isometric view of a non-invasive energy delivery devicecomprising multiple microwave antennas electrically connected to amicrowave generator according to one embodiment.

FIG. 5 shows a cross-sectional side view of the non-invasive energydelivery device of FIG. 4 delivering energy into the skin.

FIG. 6A shows a monopole antenna according to one embodiment.

FIG. 6B shows a dipole antenna according to one embodiment.

FIG. 6C shows a helical antenna according to one embodiment.

FIG. 6D shows a loop antenna according to one embodiment.

FIG. 6E shows a monopole antenna with a conductive shield or sleeveaccording to one embodiment.

FIG. 6F shows an antenna having a shaped outer conductor according toone embodiment.

FIG. 6G shows an antenna having a shaped outer conductor according to asecond embodiment.

FIG. 7A shows a cross-sectional view of an antenna having an innerconductor disposed within a coaxial cable according to one embodiment.

FIG. 7B shows a coiled antenna having a coiled conductor element formedentirely from a coaxial cable according to one embodiment.

FIG. 7C shows a coiled antenna having a coiled conductor element formedfrom an inner conductor according to one embodiment.

FIG. 8 shows a needle injecting fluid near the base of a sweat gland andtarget tissue according to one embodiment.

FIGS. 9A-9F show a number of possible configurations of bipolarelectrodes with respect to a desired treatment zone.

FIG. 10 shows an RF delivery device having one or more energy deliveryelements comprising electrode-tip needles, microneedles or stylets forinsertion into the skin according to one embodiment.

FIG. 11 shows an energy delivery device comprising a needle configuredfor percutaneous insertion according to one embodiment.

FIG. 12A shows a cryogenic system configured to have an interstitialelement comprising at least two concentric tubes according to oneembodiment.

FIG. 12B shows a cryogenic system configured to have an interstitialelement configured with a tubular coil residing inside the element.

FIG. 12C shows a cryogenic system configured to have an interstitialelement configured with a tubular coil residing partially inside andpartially outside the element.

FIG. 12D shows a cryogenic system configured to have an inner portionand outer portion such that nitrous oxide gas exits the distal portionof the inner tube and absorbs thermal energy from the distal portion ofthe outer tube.

FIG. 12E shows the injection of a cryoprotective agent according to oneembodiment.

FIG. 12F shows a zone of protected non-target tissue between a coldsource at the skin surface and the cryogenic treated region of targettissue according to one embodiment.

FIG. 13 shows a layer of colored bioresorbable microspheres depositedinto or around target tissue according to one embodiment.

FIG. 14 shows a carrier solution being introduced by a hollow needleinto a planar interface between the dermal layer and subcutaneous layeraccording to one embodiment.

FIGS. 15 and 15A show needles comprised of at least one chromophore ontheir tips according to one embodiment.

FIG. 16 shows a microneedle configuration having a non-detachablechromophore tip according to one embodiment.

FIG. 17 shows topically-applied aluminum ion particles migrating down asweat gland duct.

FIG. 18A shows a microneedle patch according to one embodiment.

FIG. 18B shows an ultrasonic transducer emitting waves as part of anultrasound treatment according to one embodiment.

FIG. 18C shows a planar ultrasonic transducer emitting waves as part ofan ultrasound treatment according to one embodiment.

FIG. 19 shows the thermal disablement of sweat glands using a controlledchemical reaction according to one embodiment.

FIG. 20A shows a sweat duct.

FIG. 20B shows the sweat duct of FIG. 20A having a layer of insulationaccording to one embodiment.

FIG. 20C shows a sweat duct of FIG. 20B having a layer of insulation andbeing treated with electrical energy according to one embodiment.

FIG. 21A shows a probe equipped with a retractable blade in anon-retractable position percutaneously inserted under a sweat glandaccording to one embodiment.

FIG. 21B shows the probe of FIG. 21A having the retractable blade in aretracted position according to one embodiment.

FIG. 21C shows the probe of FIG. 21B having the retractable blade in anadvanced position from its retracted position such that the sweat glandis sheared according to one embodiment.

FIG. 22A shows a wire device having an actuator to bow out the wire intoan expanded profile according to one embodiment.

FIG. 22B shows an actuator having an outer element and inner elementaccording to one embodiment.

FIG. 23 shows a planar cutting device comprising a pinwheel cutteraccording to one embodiment.

FIG. 24 shows a wire tunneled through target tissue through twoinsertion points in the skin according to one embodiment.

FIG. 25 shows a wire configured to be inserted into target tissue andexiting the target tissue through a sole insertion point according toone embodiment.

FIG. 26A shows a tunneling instrument having an actuator according toone embodiment.

FIG. 26B shows a tunneling instrument having an actuator according toanother embodiment.

FIG. 27 shows sweat gland ducts filled with photodynamic glue accordingto one embodiment.

FIG. 28 shows biocompatible scaffolding introduced into a sweat ductaccording to one embodiment.

FIG. 29 shows a piston used to deliver pressurized gas to a sweat glandaccording to one embodiment.

FIG. 30A shows a sweat gland having liquid according to one embodiment.

FIG. 30B shows the sweat gland of FIG. 30A ruptured after the liquid hasfrozen.

FIG. 31 shows a device for causing pressure-induced necrosis in sweatglands according to one embodiment.

FIG. 32 shows a target tissue having microbubbles and microspheressubject to rupturing by an ultrasonic transducer device according to oneembodiment.

FIG. 33 shows a cross-sectional view of a target tissue having a zone ofthermal treatment according to one embodiment.

FIG. 34A shows an isometric view of a non-invasive energy deliverydevice comprising multiple microwave antennas electrically connected toa microwave generator according to one embodiment.

FIG. 34B shows a schematic view of a cooling source located remotelyfrom an energy source and energy applicator according to one embodiment.

FIG. 35A shows a needle configured with a proximal region comprising acooling element and a distal end comprising an electrode tip accordingto one embodiment.

FIG. 35B shows an energy delivery device element comprising a metalelectrode, an inner tube and an outer circumferential surface accordingto one embodiment.

FIG. 36 shows an energy delivery device comprising a bipolar pair ofneedle-tipped electrodes according to one embodiment.

FIG. 37A shows a cooling electrode comprising a heat sink positionedbetween two pairs of bipolar needle electrodes according to oneembodiment.

FIG. 37B shows cooling electrodes in an alternating sequence withmonopolar electrodes according to one embodiment.

FIG. 38 shows a side view of a vacuum pulling and holding skin accordingto one embodiment.

FIG. 39 shows a needle comprising an energy delivery element accordingto one embodiment.

FIG. 40 shows a side view of a vacuum pulling and holding skin implantedwith electrodes according to one embodiment.

FIG. 41 shows an example of a typical skin fold.

FIG. 42 shows a skin fold being treated by an energy delivery devicecomprising two energy delivery elements according to one embodiment.

FIG. 43A shows a minimally-invasive RF delivery device comprising one ormore needles for insertion into a skin fold according to one embodiment.

FIG. 43B shows a minimally-invasive microwave delivery device comprisingone or more microwave antennas for insertion into a skin fold accordingto one embodiment.

FIG. 43C shows a minimally-invasive cryogenic therapy device comprisingone or more injection needles, catheters, stylets, cannulas or cathetersaccording to one embodiment.

FIG. 44 shows an energy delivery device according to one embodimentinserted through an edge of a skin fold and positioned along thelongitudinal axis of the fold.

FIG. 45 shows an energy delivery device according to one embodimentinserted at the top of a skin fold.

FIG. 46A shows an array of monopolar electrode needles used to delivertreatment along the longitudinal length of a skin fold according to oneembodiment.

FIG. 46B shows an array of monopolar electrode needles used to delivertreatment along the longitudinal length of a skin fold according toanother embodiment.

FIG. 47A shows an energy delivery device inserted at the top of a skinfold after a needle and blunt dissector electrode are inserted accordingto one embodiment.

FIG. 47B shows an energy delivery device inserted at the top of a skinfold after a needle and blunt dissector electrode are inserted accordingto an alternate embodiment.

FIG. 48 shows one or more paddle elements connected to a vibrationsource removably coupled to each outer side of a skin fold according toone embodiment.

FIG. 49 shows a skin fold being treated by two ultrasonic transducerspositioned on two sides of the skin fold according to one embodiment.

FIG. 50A shows an ultrasonic delivery instrument used to deliverultrasound treatment on one side of a skin fold according to oneembodiment.

FIG. 50B shows light energy being radiated to the skin fold from oneenergy source according to one embodiment.

FIG. 51 shows a perspective view of a suction electrode comprising ahousing, a tissue chamber, a vacuum port and electrodes according to oneembodiment.

FIG. 52A shows a perspective view of a clamp used to create and hold askin fold according to one embodiment.

FIG. 52B shows a side view of a clamp used to create and hold a skinfold according to a second embodiment.

FIG. 52C shows a side view of the clamp of used to create and hold askin fold according to a third embodiment.

FIG. 53 shows an array of electrodes configured to deliver energyaccording to one embodiment.

FIG. 54 shows one embodiment of a representative grid indicating targettreatment sites “A” and target treatment sites “B” that could be usedover a skin area to identify specific areas of treatment.

FIG. 55A-E show a variety of patterns illustrating specific areas oftreatment and non-treatment sites that could be used over an area ofskin.

FIG. 56 shows three templates to be used in a staged treatment, whereineach template is configured to allow treatment to a different portion ofthe overall treatment area according to one embodiment.

FIG. 57 shows a single template pattern represented by differentchromophores corresponding to different stages of treatment according toone embodiment.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS Overview of Treatments

Sweating is both a normal thermoregulation process for human beings anda normal physiological response to a psychological stress or emotionalstimuli. For most people, sweating is only a minor cosmetic annoyance.For others, however, sweating may be excessive and abnormal and,consequently, become a socially embarrassing condition. Some embodimentsof the present invention relate to methods for reducing sweat productionvia the removal, disablement, incapacitation or destruction of sweatglands in the subcutaneous tissue of a human being.

Hyperhidrosis is a clinically diagnosed disorder in which there isexcessive secretion of sweat from the sweat glands. The excessivesweating, which is thought to result from the over activity of thesympathetic nervous system, usually occurs in the palms, soles, andaxillae. Palmar hyperhidrosis is a condition of excessive sweating inthe hand. This condition is often exhibited in cold, wet handshakes.Plantar hyperhidrosis is a condition of excessive sweating in the foot.This condition may cause blisters and fungal infections. Axillaryhyperhidrosis is a condition of excessive sweating in the armpit. Suchexcessive sweating is not only socially embarrassing, but may even causestaining and rotting of clothes.

The sweat glands in the body are comprised of the apocrine and eccrineglands. Eccrine sweat glands, which lie superficially in the dermislayer of the skin, are located all over the body so that they cansecrete sweat to regulate body heat and temperature. Apocrine glands,which exist within the subcutaneous tissue and border on the interfacebetween the subcutaneous tissue layer and dermal layer, secrete an oily,milky, protein-rich product into the follicles. Bacterial digestion ofapocrine sweat is largely responsible for osmidrosis or bromohidrosis(i.e., body odor), which can be most pronounced in the foot and underarmarea.

There are various treatments used for treating hyperhidrosis. Forexample, chemical antiperspirants and deodorants are commonly used as amatter of personal hygiene. Antiperspirants are aluminum based saltsthat mechanically block the sweat gland ducts, thereby preventing sweatfrom reaching the skin surface. Deodorants change the pH of the skinsurface, thereby minimizing the presence of smell inducing bacteria.Because the effects of both of these products are temporary and canirritate the skin in some users, these products are suboptimal solutionsto cases of excessive sweating.

In addition to antiperspirants and deodorants, other topicalpreparations have been used to treat hyperhidrosis. For example,glutaraldehyde and tannic acid have been used in the treatment ofplantar and palmar hyperhidrosis. However, these treatments havegenerally lost favor because they may cause an unsightly browning of theskin.

Anticholinergic drugs have also been applied both topically andsystemically to treat hyperhidrosis. These agents block the sympatheticstimulation of the eccrine glands by inhibiting the action ofacetylcholine at the nerve synapse. Use of these drugs is limitedbecause of the systemic side effects they can cause, including, drymouth, urinary retention, constipation, and visual disturbances such asmydriasis and cycloplegia. Moreover, topical anticholinergics sometimeshave difficulty absorbing into the skin in sufficient quantities toaffect the cholinergic nerve endings.

Some patients with hyperhidrosis have resorted to surgical treatmentssuch as sweat gland excision and thoracic sympathectomy. For example,U.S. Pat. No. 5,190,518 to Takasu, which is herein incorporated byreference in its entirety, discloses an ultrasonic surgical device fordisabling and excising sweat glands. These treatments may provide for alonger duration of alleviation from hyperhidrosis. However, thesetreatments are rarely indicated due to their invasive nature, adverseconsequences and cost. For example, surgery may cause contractures ofthe skin, muscle or other surrounding tissue. Sympathectomy may resultin complications including infection, pneumothorax, Horner's syndrome,and compensatory hyperhidrosis of the trunk, back and thighs.

Recently, botulinum type-A neurotoxin (e.g., BOTOX™) has provedeffective in treating hyperhidrosis in some patients. BOTOX is commonlyused by dermatologists to denervate the neuroglandular junctions betweenthe autonomic nerves and the sweat glands. With the nerve connectionsdisabled, acetylcholine is prevented from reaching the eccrine sweatglands, thereby disabling a component of the hyperhidrosis patient'soveractive sympathetic nervous system. This treatment, however, is notwithout its downsides. Botulinum toxin is one of the most lethalsubstances on earth and, consequently, injecting it in a patient's bodyis full of risk. Additionally, since the apocrine sweat glands areinnervated by adrenergic nerves, which are not blocked by botulinumtoxin, injections of botulinum toxin do not have a clinical impact onthe body odor caused by the secretions from apocrine glands. Botulinumtoxin treatment also requires multiple, painful injections with aneedle. Furthermore, the results of this treatment last only a fewmonths, thereby necessitating repeated costly and painful treatments.

In light of the shortcomings of the aforementioned approaches, aminimally-invasive, convenient, effective, long-lasting treatment withfew side effects would be a desirable alternative for treatinghyperhidrosis.

Discussion of Anatomy

FIG. 1 is an isometric view of a cross-section of the skin, its internalstructures and surrounding tissue. The skin comprises three principallayers, the epidermis 102, dermis 101 and subcutaneous tissue 100. Theepidermis 102 is the thin, epithelial surface of the skin. The epidermis102 is comprised of several sub-layers, including, the stratus corneum,keratinocytes layer and basal layer. The epidermis 102 also containsmelanin producing melanocyte cells, which are responsible for skinpigmentation. The thickness of the epidermis 102 ranges from 0.05 mm to1.5 mm depending on the location of the skin on the body.

The dermis 101 is the middle layer of the skin and is composed of bloodvessels, lymph vessels, hair follicles, sebaceous glands, eccrine glandsand, occasionally, apocrine glands. The dermis 101 is held together byfibroblast cells that may be present as collagen protein, elastic tissueand/or reticular fibers. The dermis 101 layer also contains neuralreceptors corresponding to the pain and touch senses. The dermis 101varies in thickness depending on the location of the skin. The thicknessof the dermis 101 can range from 0.3 mm at the eyelid to 3.0 mm on theback.

The subcutaneous tissue 100 is a layer of fat and connective tissue thathouses larger blood vessels and nerves. While apocrine glands willsometimes be located in the dermis layer of the skin, it is more commonfor these glands to reside in the subcutaneous tissue. This layer 100provides a thermal barrier to help conserve body heat and additionalcushion to protect the organs from injury due to trauma. Beneath thesubcutaneous layer lies the muscular frame of the body.

Eccrine glands are distributed over the entire body surface with adensity ranging from 50 glands per square centimeter to 200 glands persquare centimeter. These glands are most densely located on the palms ofhands, soles of feet, forehead and underarms. An eccrine gland comprisesthree distinct portions: (1) the intraepidermal portion, (2) theintradermal duct (coiled and straight duct), and (3) the secretoryportion (coiled gland). The coiled gland is located in the deep dermisor at the border of the dermis 101 and subcutaneous layer 100. Theintradermal duct extends upward from the coiled gland through the dermis101, first as the coiled duct, and then as the straight duct. Thestraight duct ends as it enters into the epidermis 102 and then spiralsas it continues through the epidermis 102 and opens directly onto theskin surface.

Human eccrine sweat is composed of water, sodium, potassium lactate,urea, ammonia, serine, ornithine, citrulline, aspartic acid, heavymetals, organic compounds, and proteolytic enzymes. Generally, theconcentration of sodium in eccrine sweat varies from 35-65 mmol/l.

The eccrine glands are controlled by sympathetic cholinergic nerveswhich are controlled by the hypothalamus. The hypothalamus senses coretemperature directly and also obtains input from temperature receptorsin the skin. Production of eccrine sweat is initiated by thehypothalamus through postganglionic fiber production of acetylcholine.

Apocrine glands are primarily present in the armpits and around theanogenital areas. These glands are comprised of: (1) a coiled gland inthe deeper parts of the dermis or at the junction of the dermis andsubcutaneous fat; and (2) a straight duct which traverses the dermis andempties into the isthmus (uppermost portion) of a hair follicle. Thelumen of the coiled portion of the apocrine gland is approximately tentimes the diameter of its eccrine counterpart. The straight duct runsfrom the coiled gland to the isthmus of the hair follicle and isvirtually identical in appearance to the eccrine straight duct.

Emotional stressors stimulate the sympathetic adrenergic nerves, whichinitiate the release of viscous, fatty sweat from the apocrine glands.The amount of sweat produced by these glands is significantly smallerthan that produced by the eccrine glands. Although odorless initially,apocrine sweat develops an odor when it comes into contact with thesurface of the skin, wherein surface bacteria breaks down the organiccompounds in the sweat and produces an odor.

Another type of sweat producing glands, the apoeccrine glands, aresometimes found in the axillae (underarms). These hybrid sweat glandsare most commonly found in hyperhidrosis patients and are thought toplay a role in axillary hyperhidrosis. Their secretory portion has botha small diameter portion similar to an eccrine gland, and a largediameter portion which resembles an apocrine gland. These glands aresimilar to eccrine glands in that they respond mainly to cholinergicstimuli, and their ducts are long and open directly onto the skinsurface. However, apoeccrine glands secrete nearly ten times as muchsweat as eccrine glands. Other non-limiting examples of tissuestructures and medical conditions that may be treated using systems,methods, devices of some embodiments disclosed herein are described, forexample, at pp. 1-10 of U.S. Provisional App. No. 61/013,274 which isincorporated by reference in its entirety.

Overview of Methods and Apparatuses

Embodiments of the present application relate to methods and apparatusesfor reducing sweat production via the removal, disablement,incapacitation or destruction of apocrine and eccrine glands in thedermal and subcutaneous tissue. It is envisioned that many mechanismsand modalities can be implemented individually or in combination toachieve a reduction in sweat production in a patient. It is contemplatedthat the treatments disclosed herein could be applied to any part of thebody that is responsible for or contributes to the production, secretionand/or presence of sweat.

In one approach for reducing sweat production, a target area on a targetpatient is first identified. More preferably, particular sweat glands oran area containing such sweat glands may be identified, and the sweatglands and/or surrounding tissue can be treated with energy. This energycan take many forms (e.g., electromagnetic, microwave, radiofrequency,laser, infrared, ultrasound, etc.) and can be delivered any number ofways (e.g., topically, minimally-invasively, etc.). Additionally, thedevices employed in an energy treatment may include one or moreelectrodes, antennas, transducers, needles, probes, catheters,microneedles and stylets. Some of the other thermal treatments that canbe employed include inductive heating, resistive heating, hyperthermicchemical reactions and/or cryogenic therapy.

In combination with the thermal treatments disclosed herein, protectivetreatments can be employed to prevent damage or pain to non-targettissue. In one embodiment, thermal protective treatments may be used.For example, surface cooling can be applied to protect the epidermallayer and portions of the dermal layer of the skin while deeper regionsof skin tissue are heated via energy delivery. Various types of activeand passive cooling or heating can be configured to provide this thermalprotection to non-target tissue.

There are also numerous mechanical approaches for reducing sweatproduction. For example, the sweat glands can be surgically excised,sheared using various wires and/or blades, sealed and plugged shut,ruptured under pressure and disabled via acoustic cavitation.

A reduction in sweat production may be facilitated by administering manyof the treatments disclosed herein in one or more spatial configurationsor skin geometries. For example, treatment can be directed perpendicularto the skin surface, parallel to the skin plane or at some angle inbetween. Additionally, treatment can be administered to skin in a flat,planar configuration, in an elevated orientation or in a foldedgeometry.

A reduction in sweat production may also be facilitated by administeringtreatment over multiple stages and in a patterned arrangement. Thisapproach can enhance the body's healing response, making for a quickerrecovery with fewer complications. Various templates are disclosed toassist in administering a staged and patterned treatment.

With reference to the drawings disclosed in this specification, theparticulars shown are by way of example and for purposes of illustrativediscussion of certain embodiments. In this regard, not all structuraldetails may be shown in detail. Accordingly, it should be understoodthat the invention is not limited in its application to the details ofconstruction and the arrangement of components set forth in thedescriptions or illustrations provided herein. Additionally, it shouldbe understood that the terminology used herein is for the purpose ofdescription and should not be regarded as limiting.

FIG. 2 shows a cross-sectional view of the skin, its three primarylayers and internal structures. In one embodiment, it is desirable toconcentrate the treatment within the region of dermal 101 andsubcutaneous tissue 100 (hypodermis) in which the eccrine and apocrineglands reside (e.g., “target tissue” 105) while doing minimal damage tothe tissue above the sweat glands in the epidermis 102 and dermis 101(e.g., “superficial non-target tissue” 103) and fat cells and otherstructures within the subcutaneous layer 100 (e.g., “deep non-targettissue” 104). Depending on the area of the body, the target tissue 105region may begin anywhere from about 0.5 mm to about 4 mm beneath theskin's surface and end anywhere from about 1 mm to about 10 mm beneaththe skin's surface. Depending on the area of the body, the superficialnon-target tissue 103 region may begin at the skin surface and endanywhere from about 0.5 mm to about 4 mm beneath the skin's surface.Depending on the area of the body, the deep non-target tissue region 104may begin anywhere from about 1 mm to about 10 mm beneath the skin'ssurface.

In the case of the axillae (underarm), the target tissue region maybegin anywhere from about 1 mm to about 3 mm beneath the skin's surfaceand end anywhere from about 3 mm to about 8 mm beneath the skin'ssurface. Therefore, a treatment that concentrates energy from about 1 mmto 8 mm beneath the skin's surface in the axillae would be beneficial intreating axillary sweating.

For the purposes of this specification, eccrine glands, apoeccrineglands, and apocrine glands may be separately or collectively referredto as sweat glands or target structures. Similarly, the terms treatment,treatment effect, treating area/region may relate to the treatment ofthe target tissue and/or any target structures residing therein for thepurpose of temporarily or permanently reducing or halting sweating,wherein the treatment itself may impact the target tissue and/or targetstructures in one or more of the following ways: modification,deactivation, disablement, denervation, damage, electroporation,apoptosis, necrosis, coagulation, ablation and destruction.

It should be noted that although the methods and apparatuses discussedherein are directed to the reduction of sweat production in sweatglands, the disclosed methods and apparatuses can be modified, and maybe used for treating various kinds of target tissue and non-targettissue regions within the skin. For example, it is believed that thetreatments disclosed herein can be used to, in certain embodiments, (1)tighten skin, reduce wrinkles and contour the skin by treating collagen,induce collagen formation and/or shrink collagen, (2) treat acne bytargeting sebaceous glands within the dermis layer of the skin, (3)stimulate or retard hair growth, or temporarily or permanently removehair by treating hair follicles and/or (4) treat cellulite for thepurposes of weight loss and/or body sculpting.

Specific Embodiments A. Energy Transfer Treatment

One approach for reducing sweat production includes thermally treatingtarget tissue by either delivering energy to or extracting energy fromthe target tissue. A system can be configured to include a processor, anenergy generator connected to the processor, and a device operativelycoupled to the generator. The device can further include an energydelivery applicator or energy delivery element for delivering energy tothe target tissue. In the illustrated embodiment, a cable electricallyconnects the device to an energy generator. In other embodiments, theprocessor, the device, and/or the energy generator can be connectedwirelessly via, for example, radio frequency signals.

For purposes of this specification, the terms “electrode”, “antenna”,“energy”, “energy element”, “energy delivery element”, “energy deliveryapplicator” or “energy source” individually and collectively encompass,but are not limited to, the use of one or more types of energy transfermodalities, including electromagnetic, x-ray, radiofrequency (RF), DCcurrent, AC current, microwave, ultrasound (including high intensityfocused ultrasound (HIFU)), radiation, near infrared, infrared,light/laser, cooling and cryotherapy, adapted and applied in ranges,intensities and/or quantities sufficient to treat, directly orindirectly (e.g., heating an intermediary substance) the target skintissue via thermally or by other means. It should be noted that althoughone specific modality may be disclosed in a particular embodiment, theembodiment can be adapted to accommodate other forms of energy transfer.Even if a mechanism of energy transfer differs significantly from thatdisclosed in an illustrated embodiment, it should be understood thatsuch mechanism can be employed by this embodiment. For example, theenergy generator in one embodiment can generate an electric signalhaving a desired frequency, amplitude, and power level, and the cablecan transmit the generated signal to the device, which comprises anelectrode. In this embodiment, the processor is in communication withthe energy generator to control the power output of the energy generatorfor providing the desired amount of energy to heat the target tissue.Alternatively, in an embodiment where the device comprises a Peltierelectrode, the energy generator can supply the device with voltage tothermoelectrically cool the target tissue.

In embodiments relating to the delivery of thermal energy, in oneembodiment it would be desirable to reach a temperature of at leastabout 50 degrees C. in the target tissue and/or target structurestherein to achieve a treatment effect. For example, it is believed thatdelivering thermal energy sufficient to heat the target tissue to about60 degrees C. would likely result in thermal ablation of the targettissue. In embodiments relating to cooling the target tissue, it isbelieved that cooling the target tissue from about 0 degrees C. to −40degrees C. would likely result in a treatment effect to the targettissue.

Microwave Energy Delivery Device

The system illustrated in FIGS. 3A and 3B show a device 110 having anenergy applicator 111 for non-invasively delivering microwave energy 112to the target tissue layer 105 and a microwave generator 113 forsupplying the applicator 111 with microwave energy 112. In thisembodiment, the energy applicator 111 comprises one or more antennas fordelivering microwave energy 112 to the target tissue 105. The antennaswould be configured, when the device 110 is placed against or near thepatient's skin, to heat and treat the target tissue 105 and targetstructures within the target tissue 105. The treated tissue could eitherbe left in place to be resorbed by the body's immune system and woundhealing response, or could be extracted using any number of minimallyinvasive techniques. As illustrated, the antenna may also comprise ahorn shape, as described below, to provide a directional component tothe energy field. In one embodiment, the energy generator 113 isremotely located from the energy applicator 111, wherein the generator113 can be either stationary or mobile. Alternatively, the applicator111 and generator 113 can be coupled such that they comprise a portableunit. Still alternatively, the applicator 111 and generator 113 can becombined into a single unit.

Microwave energy is absorbed by the tissue in a process calleddielectric heating. Molecules in the tissue, such as water molecules,are electric dipoles, wherein they have a positive charge at one end anda negative charge at the other. As the microwave energy induces analternating electric field, the dipoles rotate in an attempt to alignthemselves with the field. This molecular rotation generates heat as themolecules hit one another and cause additional motion. The heating isparticularly efficient with liquid water molecules, which have arelatively high dipole moment.

The delivery of energy to the target tissue can be facilitated byantenna designs that incorporate a dielectric element. Unlike otherforms of electrical energy delivery, such as radiofrequency, whereenergy is typically transmitted through direct electrical contactbetween a metal conductor and body tissue, microwave energy can bedelivered across a dielectric material. A dielectric element will notblock the microwave energy from radiating to adjacent tissue, but it mayhelp optimize the delivery of energy to the target tissue over thecourse of the treatment. Since the dielectric heating properties andthermal conductivity of skin tissue change over the course of thetreatment (e.g., as temperature rises) due to loss of moisture, adielectric that is properly matched to the antenna design can maintainthe delivery of energy to the target tissue.

The dielectric's impact on the antenna's energy delivery properties willdecrease the further it is from the antenna. Therefore, to optimizeenergy delivery to target tissue over the course of the treatment, inone embodiment, it may be desirable to place the dielectric directlynext to the antenna rather than locating it remote from the antenna.Therefore, the antenna design could be optimized by incorporating acovering comprising a dielectric (e.g., ceramic, PTFE, polyimid, etc.)with a dielectric constant that's matched to the heating requirements ofthe treatment. The dielectric may be incorporated into the antenna or bea separate component of the energy delivery device or system. Furtherdetails regarding antenna designs are discussed below.

FIG. 4 is an isometric view depicting a non-invasive energy deliverydevice 117 comprising multiple microwave antennas 120 electricallyconnected to a microwave generator 113. In one embodiment, the antennas120 are contained in a substantially planar applicator plate 121 sizedfor application against a target area of a patient's skin 119. In oneembodiment, the device 117, and the applicator plate 121 therein, can besized and configured to substantially match the area of tissue beingtreated. For example, in treatments relating to the reduction ofaxillary sweating, the device 117 can be configured to coversubstantially all of the axillae region of the patient. Alternatively,the device 117 can be configured to cover at least a portion of theaxilla. Additionally, the applicator plate 121 may be flexible to helpthe device 117 conform to the contours of the patient's skin 119.

FIG. 5 is a cross-sectional side view of the same device of FIG. 4showing the delivery of energy 112 into the skin. In such multi-antennaembodiments, it may be useful to orient the antennas 120 along the sameplane in the same longitudinal direction to deliver energy 112 in aplanar fashion. As shown in FIGS. 4 and 5, four or five microwaveantennas 120 are positioned parallel to each other. In otherembodiments, fewer or greater microwave antennas 120 may be provided,for example, one, two, three, five, six, seven, eight, nine, ten ormore. With this planar configuration, energy can be delivered to alarger area of tissue in one treatment and in a more consistent fashion.

As discussed later in this specification, thermal protective measurescan be employed in conjunction with thermal treatments. As shown inFIGS. 4 and 5, the applicator plate 121 containing the antennas 120 maybe connected by a conduit 114 to the microwave generator 113, withcooling fluid passing through the conduit 114 to and from the applicatorplate 121 from a coolant circulator 118. The cooling fluid creates aprotected zone in the epidermis 103 of the patient, so that that targettissue 105 below the protected zone is treated.

The amount of energy 112 delivered to the target tissue 105 andconsequent extent of treatment effect can be adjusted based on thenumber of antennas 120, their specific configuration and the powerdelivered to each antenna. In one embodiment, a microwave generator 113with a microwave energy 112 output frequency ranging from 300 MHz to 20GHz is suitable for feeding the energy delivery device 117 with power.In another embodiment, a microwave signal of anywhere from about 915 MHzto about 2450 MHz would be preferential for yielding a treatment effecton tissue. Alternatively, a signal having a frequency ranging from about2.5 GHz to about 10 GHz may also be preferential. Additionally, solidstate, traveling wave tube and/or magnetron components can optionally beused to facilitate the delivery of microwave energy 112.

With respect to antenna design, FIGS. 6A to 6G illustrate severalpossible variations that can be implemented to achieve the energydelivery function disclosed herein. In each design, the antennacomprises the distal end of a coaxial cable feedline through whichelectrical energy is transferred from an energy generator. The coaxialcable further comprises an inner conductor shaft 124 and outer conductor125. FIG. 6A shows one embodiment of a monopole antenna 122. As shown inFIG. 6E, the antenna may be shielded or choked by a metal 127 to limitthe electromagnetic field propagated by the antenna. In such monopolarconfigurations, an inner conductor element 123 extends from the innerconductor shaft 124 and beyond the outer conductor 125 such that theelectromagnetic field propagated by the antenna originates from only theinner conductor element 123. In dipole antenna 128 configurations, asillustrated in FIG. 6B, the outer conductor 125 is exposed in such amanner that an electromagnetic field is created between the innerconductor element 123 and outer conductor 125.

Depending on the performance desired of the antenna, the antenna mayoptionally comprise a helical antenna 129 (FIG. 6C), loop antenna 130(FIG. 6D) or horn antenna 131 (FIGS. 6F and 6G). These alternativeantenna configurations provide geometric radiating patterns. Forexample, as illustrated in FIG. 6F, the outer conductor 125 may comprisea shaped element, such as a horn shape, to provide a directionalcomponent to the field created between the inner conductor element 123and outer conductor 125. Optionally, the outer conductor element 125and/or inner conductor element 123 may be bordered by, coupled to orcoated by a dielectric element to optimize the energy deliverycapabilities of the antenna.

In another embodiment relating to energy delivery to target tissue, theenergy applicator comprises an antenna connected to a coaxial cable thatis coupled to a microwave power source. As illustrated in FIG. 7A, theantenna 132 further comprises an inner conductor disposed within thecoaxial cable 133, wherein an inner conductor element 123 extends beyondthe distal end of the coaxial cable 133 to form a coiled conductorelement. The coiled conductor element provides a relatively flatstructure which can be aligned with the skin surface to deliver an evenamount of energy to a plane of target tissue. The applicator mayoptionally further comprise at its distal end a thin shield comprised ofa polymer or ceramic. FIGS. 7B and 7C illustrate additional embodimentsof the coiled antenna configuration, wherein the coiled conductorelement may comprise either the coaxial cable 133 or just the innerconductor 123.

Note that FIG. 7A shows the use of cooling fluid flowing through acoaxial antenna system 132. This antenna embodiment, or any otherantenna configuration previously shown, for example FIG. 6E, can beconfigured to not only cool the skin, but also to create an area oflower pressure inside the device chamber than in the ambientsurroundings. This area of lower pressure or suction within the devicewill help (1) adhere the device to the skin, bringing the target tissueinto closer apposition to the antenna, and (2) reduce blood flow in thetarget tissue, thereby enabling more efficient heating of the tissue.

Additionally, suction may help to control pain by triggering stretch andpressure receptors in the skin, thereby blocking pain signals via thegate control theory of pain management. The gate control theory holdsthat an overabundance of nerve signals arriving at the dorsal rootganglion of the spinal cord will overwhelm the system, and mask or blockthe transmission of pain receptor signals to the brain. This mechanismof pain management is exploited by implantable electrical pain controlsunits, TENS systems, the Optilase system and others.

Since microwave heating is particularly efficient when water moleculesare present in tissue, it may be desirable to have relatively high watercontent or molecule density at the target tissue or within the targetstructures. This high water content would result in greater microwaveenergy absorption and consequent heating at the point of treatment.Moreover, this phenomenon will allow the selective heating of targettissue, thereby minimizing the impact to non-target tissue.

There are numerous ways in which water content in the target tissue canbe achieved. For example, injecting a bolus of fluid (e.g., water,saline, etc.) into the target tissue or target structures would rendersuch areas more susceptible to microwave treatment. FIG. 8 shows oneembodiment of the injection of fluid 116 to near the base of a sweatgland and target tissue 105. In the case of target sweat glands, thepatient can be induced to sweat in the area of treatment (such as byraising the ambient temperature or the temperature in the target area)in order to achieve higher water content in the target structures. Inany of these cases, the water dense sweat glands can be plugged toprevent any of the water/sweat from escaping through the sweat ducts.Sealing the gland ducts can be achieved by using aluminum ion basedtopical products such as antiperspirants or any type of biocompatiblepolymer coating.

Further non-limiting examples of embodiments and components ofembodiments of microwave systems, devices, and methods that can beutilized with those described herein are described, for example, inFIGS. 3-9 and 20-26 and pp. 11-20 and 34-48 of U.S. Provisional App. No.61/013,274 previously incorporated by reference in its entirety, as wellas FIGS. 1-25 and pp. 9-18 and pp. 56-69 of U.S. Provisional App. No.61/045,937, also previously incorporated by reference in its entirety.Furthermore, embodiments and components of embodiments described hereinas well as, for example, those discussed in the previous sentence can beused to generate tissue profiles as illustrated in FIGS. 26-51 anddescribed in pp. 18-39 of U.S. Provisional App. No. 61/045,937,previously incorporated by reference in its entirety.

RF Energy Delivery Device

Radiofrequency (RF) energy is another mode of electromagnetic energydelivery that can be used to treat the target tissue. In one embodiment,a device comprising at least one electrode for delivering an electricfield therapy is operatively connected to an RF generator for deliveringRF energy via the electrode to target tissue. The energy delivery mightbe continuous or pulsed, thermal or non-thermal. For example, acontinuous or pulsed electric field delivered from the electrode canheat the target tissue to a temperature necessary to achieve a desiredtreatment effect. Alternatively, the delivered energy can heat and/orablate the nerves, neuromuscular junctions and/or neuroglandularjunctions associated with the target structures in order to temporarilyor permanently denervate the target structures. A pulsed electric fieldcan also induce electroporation in these neural structures or the targetstructures themselves to achieve a treatment effect.

The electrode(s) can be individual electrodes that are electricallyindependent of each other, a segmented electrode with commonly connectedcontacts, or a continuous electrode. A segmented electrode can, forexample, be formed by providing an insulated tube with slots into whichthe electrode is placed, or by electrically connecting a series ofindividual electrodes. Individual electrodes or groups of electrodes canbe configured to provide a bipolar signal. The electrodes can bedynamically assignable or hardwired to facilitate monopolar and/orbipolar energy delivery between any of the electrodes and/or between anyof the electrodes and one or more external ground pads. For example, anarray of electrodes can be configured such that both a monopolar energyfield and a bipolar energy field can be selectively, sequentially,and/or simultaneously delivered. A ground pad can, for example, beattached externally to the patient's skin (e.g., to the patient's leg).

There are a wide variety of configurations for the active electrodes ineither monopolar or bipolar configurations. They may be flat or curvedto promote uniform contact over the electrode surface. The contact areaof the active electrodes may be round (e.g., circular, elliptical) orrectilinear (e.g., square, rectangular, polygonal)—virtually any shapeis possible. The shape may be chosen, for example, to suit the tissue tobe treated or to allow optimal coverage for repeated activations. Forexample, in one embodiment, an electrode with a hexagonally shapedcontact area may offer the advantage of providing complete coverage whentreating irregular areas through multiple activations. It will beappreciated that similar shapes may be used for the applicator plate inthe microwave embodiments discussed above. The number of electrodes maybe varied to allow patterned delivery of energy to tissue; at least oneactive electrode for monopolar and at least two active electrodes forbipolar are desired. Multiple electrodes can be configured in manydifferent patterns such as circular patterns, radial patterns,rectangular arrays, or in approximation of any of the shapes describedin this specification. FIGS. 9A-F show a number of possibleconfigurations of bipolar electrodes 201 with respect to a desiredtreatment zone 105, including top and side views of alternatingconfiguration electrodes shown in FIG. 9A, top and isometric views ofalternating plane configuration electrodes shown in FIG. 9B, tridentconfiguration electrodes shown in FIG. 9C, sandwich configurationelectrodes shown in FIG. 9D, flat plate configuration electrodes shownin FIG. 9E, and roof with plate configuration electrodes shown in FIG.9F.

The depth of energy penetration, achieved tissue temperature andconsequent extent of tissue effect caused by the RF delivery device willdepend on a number of factors, including, the power delivered by the RFgenerator, the spacing of the one or more electrodes, the size of theelectrodes, the orientation of the electrodes, the amount of contact theelectrodes have with the target tissue and the properties of the tissueitself.

The electrical generator may be a conventional power supply thatoperates at a frequency in one embodiment in the range from about 200KHz to about 1.25 MHz, more preferably about 400 KHz to about 1.0 MHz,with a conventional sinusoidal or non-sinusoidal wave form. Such powersupplies are available from many commercial suppliers, such asValleylab, Aspen, and Bovie. Depending on the desired treatment effect,it may be necessary for the electrical generator to operate atrelatively low and relatively high voltages and power levels. Forexample, generator operability may include a power anywhere from about ½W to about 100 W. In some embodiments, to achieve the desired treatmenteffect it may be desirable to continuously deliver energy for periods asshort as ¼ second or as long as 300 seconds.

For embodiments that require the delivery of a pulsed electric field(PEF), PEF parameters may include, but are not limited to, voltage,field strength, pulse width, pulse duration, the shape of the pulse, thenumber of pulses and/or the interval between pulses (e.g., duty cycle),etc. in any range and combination. Suitable pulse widths include, forexample, widths of at least 10 seconds and up to about 500 milliseconds.Suitable shapes of the pulse waveform include, for example, ACwaveforms, sinusoidal waves, cosine waves, combinations of sine andcosine waves, DC waveforms, DC-shifted AC waveforms, RF waveforms,square waves, trapezoidal waves, exponentially-decaying waves, andcombinations thereof. Suitable numbers of pulses include, for example,at least one pulse. Suitable pulse intervals include, for example,intervals less than about 10 seconds. These parameters are provided forthe sake of illustration and should in no way be considered limiting.

In the embodiment illustrated in FIG. 10, the RF delivery device 202 cantake the form of one or more energy delivery elements comprisingelectrode-tip needles, micro-needles, or stylets for insertion into oracross the epidermal layer 102 of the skin. Alternatively, the entireenergy delivery element can comprise an electrode that is optionallyinsulated at points along the element where energy delivery isundesirable (e.g., non-target tissue). This minimally-invasive insertionapproach allows for a more localized treatment of target tissue 105 suchthat damage to non-target tissue is minimized. Following needle 203insertion to a reasonable depth, which would preferably be the depth oftarget tissue, but may be more or less deep, the operator can direct theRF generator 204 to deliver an electric field to the electrode forsubsequent delivery to the target tissue 105. The electric field fromthe electrode will resistively heat the target tissue 105. In instanceswhere the target tissue 105 is outside the electric field, and thereforeoutside the zone of resistive heating, the target tissue can be heatedconductively by adjacent tissue that is resistively heated by theelectrode's electric field.

Another potential benefit of having the interstitial needle insulatedalong its length is avoiding unnecessary heating of non-target tissuevia thermal conduction from the needle itself. As the electroderesistively heats the surrounding tissue during RF treatment, theelectrode also absorbs heat from the tissue. Heat absorbed by theelectrode may then be conducted to the rest of the needle where it maybe undesirably passed to surrounding, non-target tissue. A needle 203configured with an insulated shaft 205 as illustrated in FIG. 10 canprevent the conduction of heat to non-target tissue alongside the needleshaft 205. In this embodiment, a proximal portion of the needle isinsulated to the depth of the non-target tissue while the electrode 206at the distal portion of the needle 203 is exposed to treat the targettissue 105. Alternatively, the electrode 206 tip can be partiallyinsulated in such a fashion as to provide a directional component to thedelivery of RF energy. This directional bias may advantageously providea means for minimizing energy delivery and consequent thermal damage tonon-target tissue.

Protective treatments may be used with certain embodiments (not shown).In the case of thermal treatments such as by RF energy or microwaveenergy, a cooling system, cooling element or cooling component may beprovided such as described elsewhere in this specification. In oneembodiment, the cooling element may be used in combination with aninsulating element, while in another embodiment, the cooling element maybe used as an alternative to an insulating element. When a cryogenictreatment is provided (as described further below), a protectivetreatment may include heating a portion of an energy delivery device.

Depending on the target tissue 105 region being treated, the needleelectrodes 206 of FIG. 10 may have a length of about, for example, 1 to10 mm, and preferably no greater than about 8 mm. Even more preferably,the needle electrodes 206 may have a length of about 2 to 5 mm in someembodiments. It will be appreciated that the length of the needles 203may be optimized to be inserted to a depth where the target tissue 105is located.

In the embodiment illustrated in FIG. 11, the energy delivery devicecomprises a needle 208 configured for percutaneous insertion. The needle208 further comprises a distal portion having one or more energydelivery elements 209 for delivering energy 210 to the target tissue105. More specifically, this embodiment may comprise a needle 208 havingone or more electrodes for treating the target tissue with RF energy210. As mentioned above, a portion of the needle 208 can be insulated toprovide a directional component to the energy delivery. This directionalcomponent can advantageously allow for a more controlled treatment,wherein less non-target tissue is damaged. In one embodiment, the needle208 is insulated so that energy is delivered toward the epidermis 102and away from subcutaneous 100 tissue. The electrode 206 provided on theneedle 208 may have any suitable length to treat a single sweat gland ormultiple sweat glands. Alternatively, multiple electrodes 206 can beplaced on the needle 208 spaced apart for treating multiple sweatglands. To treat a larger area of target tissue 105, the needle 208 canoptionally be configured to translate angularly or be “fanned” outparallel to the target tissue 105. For example, the energy deliveryelement 209 can be rotably coupled to the needle 208 so that it maytranslate parallel to the target tissue 105. As discussed with previousembodiments, a cooling source may be provided on the skin to protect theskin surface, epidermis 102 and parts of the dermis 101.

Cryogenic Therapy Device

Cryotherapy may present an opportunity to provide a treatment effect ontarget tissue. Since the collagen matrix of the skin is less sensitiveto cold, it is possible to cool target structures without damagingnon-target skin tissue comprising collagen. The embodiments depicted inFIGS. 10 and 11 can also be utilized to treat the target tissue viacryotherapy. In these embodiments, an interstitial element comprisingone or more needles, stylets, catheters or probes can be configured withone or more passageways to deliver a cryogenic fluid to at least onethermally conductive element adjacent or near the target tissue toprovide treatment to the target tissue. The system can be configured tohave an adjacent or remotely located generator for supplying cryogenicfluid (e.g., liquid nitrogen, liquid helium, liquid argon, liquidcarbon-dioxide, liquid nitrous oxide, liquid AZ-50, chilled anti-freeze,chilled alcohol, chilled saline, etc.). The generator should delivercryogenic fluid to the device sufficient to reduce the temperature ofthe target tissue to between about 0 to −40 degrees Celsius. In someembodiments, a temperature of between about 0 to −10 degrees Celsius maybe sufficient to induce necrosis in the target tissue although this maybe above the freezing point of the target tissue, whereas a temperatureless than about −10 degrees Celsius may be sufficient to freeze thetarget tissue.

To maintain constant cooling therapy, it may be desirable to circulatethe cryogenic fluid through the interstitial portions of the device. Forexample, as illustrated in FIG. 12A, the device 211 is configured withan interstitial element 212 comprising at least two concentric tubes213, 214. In this embodiment, cryogenic fluid can be delivered throughthe interstitial element 212 and to the thermally conductive element bythe inner tube 213 and then circulated out of the interstitial element212 through the outer tube 214. In this embodiment, the outer tube 214itself can be a thermally conductive element. Alternatively, asillustrated in FIGS. 12B and 12C, the interstitial element 212 could beconfigured with a tubular coil 215 that resides either inside or outsideof the element 212. The cryogenic fluid would be routed through thelumen of the coil 215 to provide a thermal treatment effect to thetarget tissue.

In other embodiments, the device may comprise a cryoballoon catheter,wherein the thermally conductive element comprises a balloon. In suchballoon configurations a pressurized liquid such as nitrous oxide isrouted through the interstitial element's passageway. When the liquidreaches the balloon it undergoes an endothermic phase change such thatthe liquid absorbs heat from the surrounding area to achieve a treatmenteffect on the target tissue.

Alternatively, an interstitial needle or probe can be used instead of acryoballoon catheter to administer cryotherapy to target tissue. Forexample, FIG. 12D shows an interstitial element 212 comprising an innertube 216 and outer tube 217. The inner tube 216 comprises an inner lumen218 for liquid nitrous oxide to travel from a proximal portion 219 to adistal portion 220 of the tube. The inner tube 216 further comprises atleast one port or nozzle 221 along the distal portion 220 of the tubefor the liquid nitrous oxide to exit the inner tube 216. As the liquidnitrous oxide exits the port 221 at, preferably, high velocities, itundergoes an endothermic phase change, wherein the outer tube 217 iscooled by the nitrous oxide gas. As the gas absorbs energy from theouter tube 217, which comprises the thermal conductive element in thisembodiment, and the surrounding target tissue, the gas then exits theinterstitial element 212 through the annular space between the outertube 217 and inner tube 216.

The approach disclosed in FIG. 12D allows for a more focused area ofcryogenic treatment. The nitrous oxide gas exits the distal portion 220of the inner tube 216 at its coldest temperature and then absorbsthermal energy from the distal portion 1242 of the outer tube 217.Following heat exchange with the distal portion 1242 of the outer tube217, the gas then travels toward and out the proximal end 219 of theinterstitial element 212. Therefore, the distal portion 1242 ofinterstitial element 212, the portion which is adjacent to the targettissue, is the coolest.

Various parameters of this cryogenic system can be adjusted to modulatethe temperature of the gas and vary the rate and extent of thermaltreatment. For example, the shape, size and number of nozzle/portopenings may have bearing on the rate of conduction and convection. Thesize of the annular space between the outer and inner tubes of theinterstitial element will also impact the heat transfer properties ofthe device. Additionally, the pressure of the nitrous oxide liquid willalso contribute to the heat exchange capabilities of the treatment.

Cryotherapy may also be administered topically to treat target tissuebelow the surface of the skin. To minimize the risk of damage to theepidermis and other non-target tissue, it may be desirable to usecryoprotective agents in conjunction with non-invasive cryotherapy. Asillustrated in FIG. 12E, cryoprotective agents 222 such as ethyleneglycol, glycerol, erythritol or dimethylformamide can be appliedtopically or via injection to minimize the treatment effect tonon-target tissue 103. Cryoprotective agents 222 can also be utilized inconjunction with percutaneous therapies utilizing the interstitialelements discussed above. As shown in FIG. 12F, the cryoprotectiveagents 222 can be used to create a zone of protected non-target tissue223 between the cold source 225 at the skin surface 119 and thecryo-treated region 224 of target tissue.

Phototherapy

Another approach for treating target tissue comprises the use ofphototherapy. In this approach, the unique optical characteristics oftarget structures are used to determine a spectral signature for eachstructure. Light energy can be delivered to the target tissue at awavelength that is matched to the spectral signature of a particularstructure to selectively heat and treat the structure through lightabsorption.

Phototherapy can also be implemented through coloring the target tissueor area surrounding the target tissue and then delivering light energyto heat the coloring. For example, a colored substance can be introducedinto the target tissue and a light energy having a waveform that has aspecific absorption for this color can be delivered from an internal orexternal source to treat the target tissue. The principal advantage ofthis approach is that the target tissue can be selectively colored sothat the treatment can be localized to the target tissue with minimalimpact to non-target tissue. Phototherapy can be performed using varioustypes of light energy, including, but not limited to, laser, intensepulsed light (“IPL”), focused IP, infrared and near infrared. Thesevarious light energies can be implemented with any number of energydelivery elements, including, but not limited to, a laser, lightemitting diode (“LED”) or light bulb. Optionally, one or more filterscan be used in conjunction with any of these energy delivery elements toremove unnecessary wavelengths, including those that would be absorbedby non-target tissue.

In one embodiment associated with phototherapy, a chromophore (i.e.,colored molecule) is introduced into the target tissue. In the casewhere the target structures are the sweat glands, the chromophore can beintroduced through the gland ducts via topical delivery, injected to thetarget tissue or ingested by the patient such that the coloring appearsin the patient's sweat (i.e., chromohidrosis). For example, it is knownthat sulfur compounds in garlic are metabolized by the body to formallyl methyl sulfide (AMS), which is excreted from the body via thesweat. By binding a chromophore to the sulfur in garlic such that thechromophore is bound to AMS post-metabolization, the color can bedelivered directly to the sweat glands. Following the appearance ofcolor in the target tissue, an external source or energy deliveryelement (e.g., light emitting diode “LED”) can deliver a light energysource, such as a laser or other light delivery system specificallymatched to one or more chromophores to selectively treat the targettissue. This light energy can non-invasively travel down the sweat ductor transcend the layers of epidermis and dermis to reach the targettissue. Alternatively, an interstitial device utilizing fiber optics candeliver the light energy directly to the target tissue.

In another embodiment associated with this approach, a coloredbioresorbable element can be introduced into or around the targettissue. For example, as illustrated in FIG. 13, a layer of coloredbioresorbable microspheres 226 can be deposited into or around thetarget tissue 105. The microspheres 226 can be injected as part of abio-inert solution, gel or other carrier with a syringe 227 into oraround the target tissue 105. Once deposited in or around the targettissue 205, the colored microspheres 226 can be heated by laser light228 from a laser 229 matched to their particular color, therebyconductively heating the target tissue 105 to yield a treatment effect.These microspheres 226 can be comprised of materials, such aspolytetrafluoroethylene (PTFE), polymethyl methacrylate (PMMA) orcalcium hydroxylapatite (CaHA), and colored to match laser wavelengthsthat would result in the most efficient heating of the microspheres 226,with the laser 229 having relatively little impact on the tissue in itspath.

In phototherapies involving the deposition of chromophores into oraround the target tissue, delivering chromophores in the presence of acarrier solution may result in a wider and more even distribution ofchromophore prior to treatment. A wider and more even distribution ofchromophore may result in a wider and more consistent treatment effect.For example, chromophore may be suspended in a carrier solution ofbuffered or unbuffered saline prior to injection into the target tissue.As illustrated in FIG. 14, a carrier solution 230 is introduced using ahollow needle 231 into the planar interface between the dermal layer 101and subcutaneous layer 100 to create a pathway for chromophoremigration. Additionally, the carrier solution 230 may incorporate drugsfor enhancing the distribution and/or effects of the chromophore orfacilitating recovery following treatment.

In another embodiment associated with the phototherapy approach, aneurotoxin can be used as a vehicle to carry a colorant to theneuroglandular or neuromuscular junctions of the target tissue and/ortarget structures. It is commonly known that Clostridium botulinumneurotoxins, such as botulinum toxin type-A, can be administered totreat various neuromuscular and neuroglandular conditions by binding tocholinergic neurons at these junctions and blocking the release ofacetylcholine in the synaptic vesicles of the neurons. Although thetissue at the junction is denervated by this blocking, this result isonly temporary. By using the toxin to color the neural junctions of thetarget tissue and/or target structures, light energy can be delivered tothermally ablate these junctions and selectively denervate the targettissue/structure to achieve a longer lasting treatment.

In this approach, the toxin itself can be colored or alternatively, achromophore chemically bound to the toxin may be used. Additionally, thelight energy delivered to the target tissue will be specifically matchedto the colorant to maximize the energy absorbed at the junctions.

There are seven serologically distinct types of botulinum toxin,designated A through G. The toxin is a two-chain polypeptide with a100-kDa heavy chain (“heavy chain”) joined by a disulphide bond to a50-kDa light chain (“light chain”). The heavy chain is responsible fortargeting and binding to the cholinergic neurons at and around theinjection site and helping the light chain cross the neuron cell'smembrane. The light chain is responsible for carrying the toxicity tothe neuron. Although a potential molecular mechanism of toxinintoxication of botulinum toxin is discussed here, other toxins, forexample, butyricum toxins, tetanus toxins, exotoxins, diphtheria toxins,cholera toxins, ricin, or variants thereof may have the same orsubstantially similar mechanisms.

In this approach it may be desirable to only use the heavy chainfragment of the toxin as the colorant's delivery vehicle. By isolatingthe heavy chain fragment and excluding the light chain fragment from thetoxin molecule, the introduction of toxicity into the body will beavoided. Additionally, since an intact toxic molecule may provide atemporary treatment effect, presence of the light chain fragment maymake it difficult to determine the success of the thermal treatment.Accordingly, coloring a heavy chain toxin fragment or binding achromophore to a heavy chain toxin fragment may result in a moreappealing treatment. In some embodiments, 100 to 200 units of botulinumtoxin are administered to a patient to treat an axillary region. Otherdoses may also be administered depending on the desired clinical result.

In another embodiment, microneedle technology can be employed tofacilitate the delivery of chromophores to the target tissue. Forexample, the microneedles can be hollow to facilitate the delivery of acolored substance (e.g., liquid or solid chromophore, coloredmicrospheres, etc.) to the target tissue. Alternatively, the needles maybe configured to deliver the chromophores only across the stratumcorneum from where the chromophores can migrate to the target tissue viareverse iontophoresis. In an additional embodiment, reverseiontophoresis is used to drive the chromophores directly across theepidermis and into the deep dermis.

In another embodiment, as illustrated in FIGS. 15 and 15A, the needletips 232 are comprised of at least one chromophore 233 and areconfigured to detach from the needle 234 when inserted into or alongsidethe target tissue. The needle tip 232 may be coated with a chromophore233 or be comprised of a solid chromophore 233 and the needle shaft 235may be solid or hollow. In embodiments employing the detachable,chromophore tipped microneedles 234, the microneedles 234 can optionallybe configured to engage a tip deployment mechanism 237. A tip deploymentmechanism 237, such as a single plunger or array of plungers, can beutilized to facilitate the detachment of the chromophore needle tip 232.For example, hollow-bodied needles 234 can be used to allow thedeployment mechanism 237 access to the detachable chromophore tip 232.More specifically, the deployment mechanism 237 can be driven throughthe needle's lumen 238 to disengage the detachable tip 232.Alternatively, the deployment mechanism 237 can comprise a hydraulicelement, such as pressurized air, to effect the detachment of the needletip 232. Additionally or alternatively, the needle tip 232 and/or needleshaft 235 can be configured with a pre-established weakness tofacilitate deployment. For example, as illustrated in FIGS. 15 and 15A,the needle tip 232 can be configured with a notch or groove 236 suchthat it breaks along the notch or groove 236 following insertion into orprior to retraction from the target tissue.

The needles 234 shown in FIGS. 15 and 15A may be joined in an array ofneedles, such as a linear or planar array. The needles 234 may have alength of about 2 to 8 mm, more preferably about 4 mm, with the lengthof the detachable tip 232 being matched to the depth of the targettissue. The deployment mechanism 237 such as a plunger or array ofplungers may detach each needle separately, in a preferential sequence,or all at once.

In an alternate embodiment employing chromophore tipped microneedles,the microneedle shaft is comprised of a dissolvable material such thatthe microneedle shaft dissolves following the microneedle insertion intothe skin, leaving the chromophore tip in the target tissue. For example,a microneedle array can be cast and cured with the distal tipscomprising chromophores and the proximal shaft comprising a sucrosesolution. Once the microneedle is inserted into the skin, the sucroseshaft will be broken down within the interstitial space of the skintissue such that the chromophore tip is the only portion of the needlethat remains in the skin. In this embodiment, it may be desirable toincorporate a flexible backing substrate into the cast microneedle arraysuch that following insertion into the skin, the backing can be peeledoff the microneedle leaving a portion of the needle shaft andchromophore tip within the skin.

Optionally, the hollow microneedles can be utilized as a pathway fordelivery of light energy to the deposited colored substance from asource outside the body. Alternatively, the microneedles may comprisefiber optic material to facilitate the delivery of light to the color atthe target tissue.

In the above embodiments providing for the delivery of color to thetarget tissue, various mechanisms can be employed to minimize the impactof any structures or color fragments left behind following treatment. Inthe case of certain colored liquids, gels and solids, the laser deliverycan be set at an intensity and duration sufficient to ablate andvaporize part or all of the deposited material. In the case of abioresorbable implant, such as microspheres, the implant may eventuallybe absorbed into the surrounding tissue so there is no adversephysiological or aesthetic impact resulting from the presence of themicrospheres or color. Additionally or alternatively, any remainingcolor can be bleached by light at the treatment wavelength, or analternate wavelength, such that it is no longer visible in the skin.Alternatively, the chromophore may not be bioresorbable, or bleachable,but rather the light energy may fracture the chromophore into particlessmall enough to be phagocytosed and cleared from the body by the immunesystem. This mechanism of action is well known in the area of tattooremoval, where, for instance, carbon black tattoo inks are fractured bylaser light and cleared by the body.

In another embodiment incorporating chromophore-tipped microneedles, thechromophore tip is configured to be removed from the target tissue alongwith the needle. In this configuration the tip is not detachable fromthe needle shaft. This intact microneedle 239 configuration isillustrated in FIG. 16. The needle 239 may comprise a proximal portion240 made of an optically clear material or an optically neutralchromophore (i.e., unable to absorb, block or otherwise be activated bythe treatment wavelength) and a distal portion 241 made of achromophore. As light energy is delivered across the proximal portion240 of the needle and absorbed by the colored distal portion 241, thedistal portion 241 begins to heat, thereby conductively heating andtreating the surrounding target tissue. Alternatively, the proximalportion 240 of the needle 239 can be configured as a light pipe or lensto focus the light energy into the chromophore tip 232.

In embodiments utilizing non-detachable, chromophore-tippedmicroneedles, it may be desirable to incorporate an array of needlesinto an optically neutral backing system. This array comprisingchromophore tips and optically neutral shafts, configured with ageometry and needle density to optimize the treatment to target tissue,can be permanently coupled to an optically neutral backing system toform a microneedle patch. Following the insertion of this patch into thepatient's skin, light energy can be applied to the optically neutralbacking such that this energy is delivered via the optically neutralshafts and absorbed by the chromophore tips of the needles. The absorbedenergy will heat the chromophore tip and thereby treat the surroundingtarget tissue. The patch can be any size, shape and geometry necessaryto match the treatment area. Optionally, the patch's backing maycomprise a flexible material to allow the patch to conform to thepatient's skin. The backing system may also comprise an opticallyneutral adhesive on the portion most proximate to the skin to minimizemovement of the patch during treatment. The use of adhesive may providesignificant benefit in avoiding targeting error of treatment or patientdiscomfort from needle motion.

In any of the above embodiments relating to microneedles or microneedlepatches, it may be beneficial to incorporate a drug into the adhesive,backing, or proximal portion of the needle shaft to facilitate healingof non-target tissue. The needles or patch can optionally be leftinserted into the patient's skin following treatment of the targettissue to serve as an integral bandage. These healing drugs may comprisesteroids, non-steroidal analgesics or anti-inflammatory medications suchas antibiotic cream. Alternatively, the needle may be fully or partiallycoated with a chemical substance, such as a sclerosing agent, to enhancetreatment of the target tissue.

In embodiments incorporating a microneedle patch having opticallyneutral components, it may be desirable to configure the system to blockthe delivery of energy once a specific threshold is reached to preventunnecessary damage to the target tissue and/or non-target tissue. Forexample, an optically neutral backing, adhesive and/or needle can bedesigned such that when a prescribed amount of energy is transmittedthrough the system, at least a portion of the component becomesoptically opaque to the treatment wavelength, thereby preventingadditional energy from reaching the chromophore tips and heating thetarget tissue. Alternatively, these components can be heat ortemperature sensitive such that energy delivery is blocked once thetarget tissue or non-target tissue reaches a prescribed thresholdtemperature. Alternatively, the backing material may be configured to beopaque, blocking the light delivery to all but the proximal needleshafts, which extend through the backing material to the upper surfaceof the array system, thereby blocking light delivery to all tissueexcept those directly in contact with the chromophore tips.

In any of the phototherapy applications, it may be desirable to monitorabsorption of the light spectra within the tissue in order to detectchanges in the absorption spectra. Changes in the absorptioncharacteristics of the tissue are indicative of changes within thetissue, and can be used to detect treatment efficacy, control extent oftreatment, or confirm completion of treatment.

Inductive Heating

Another method of providing a treatment effect to target tissuecomprises inductively heating particles within or around the targetstructures. These particles are preferably metallic (e.g., iron) and ofa size that can be introduced into the target tissue region in anon-invasive or minimally invasive manner. For example, a solution ofmicro-sized ferromagnetic particles can be introduced into the targettissue via injection with a syringe. Alternatively, it may be easier toreach the target tissue using magnetic nanoparticles. Once one or moreparticles (e.g., ferromagnetic particles) are in or around the targettissue, an electromagnetic energy source from either inside or outsidethe body can generate an electromagnetic field to create a current inthe metallic particles in vivo. These currents will cause resistiveheating of the particles and the consequent conductive heating of thetarget tissue. The electromagnetic energy source can continue deliveryof energy to the particles until treatment of the target tissue iscompleted.

In the case where the target tissue is one or more sweat glands, theparticles may be introduced topically via the sweat gland ducts. As withaluminum ion particles in antiperspirants, which are sent down the sweatgland duct to block sweat from reaching the skin surface,topically-applied particles can be introduced into the sweat glandducts. As illustrated in FIG. 17, these particles 242 can migratenaturally down the duct 109 and into the coil of the gland.Alternatively, pressure can be used to facilitate the travel of theseparticles 242 to the sweat gland. Alternatively or optionally,iontophoresis may facilitate the delivery of metallic particles 242 intothe sweat glands. As mentioned above, electromagnetic energy 243 may bedelivered from an electromagnetic energy source 244 to heat theparticles 242 and surrounding target tissue 105 until the treatment iscompleted (e.g., sweat production in the sweat gland has halted and/orthe sweat gland has been thermally ablated).

It should be understood that virtually every phototherapy relating tothe delivery of color to the target tissue discussed in thisspecification can be modified to deliver metallic particles for aninductive heating treatment. For example, ferromagnetic particles can besubstituted for chromophores, ferromagnetic fluidic suspensions can beused instead of colored solutions, and ferrous-tipped microneedles canbe used in place of chromophore-tipped microneedles.

It may be desirable to remove the ferromagnetic particles from the bodyfollowing treatment. As such, a microneedle patch comprising anon-magnetic backing system, non-magnetic needle shafts (or proximalportions of the shafts) and non-detachable ferro-tipped microneedles maybe employed. Optionally, this embodiment, as illustrated in FIG. 18A,can incorporate an electromagnetic element 245 directly into the backingmaterial 1249. This electromagnetic element 245 can be any structure ormaterial, such as a metal wire, that has electromagnetic properties andis electrically connected to an energy source. The electromagneticelement or an electromagnetic source delivers a field 246 to resistivelyheat the tips 247, thereby treating the target tissue 105. Following thetreatment, the microneedle patch 248 is removed from the patient alongwith the non-detachable ferromagnetic tips 247.

Ultrasonic energy can be used as another means of treating the targettissue. For example, ultrasound hyperthermia can be induced bydelivering an ultrasonic wave to target tissue, causing the tissue tovibrate and heat. Wave frequencies between about 20 kHz and 18 MHz withpowers ranging from about 0 to 50 W/cm² can achieve these results.Treatment may be more effective at frequencies between about 0.1 MHz and3 MHz and powers from about 720 mW/cm² to 50 W/cm².

In focused ultrasound treatments, one or more ultrasonic transducersemit waves which meet at a specific focal point at a prescribed distancefrom the transducer. As shown in FIG. 18B, the convergence of thesewaves 249 from an ultrasonic transducer 251 causes an intense,cumulative effect at the focal point 250. Once each wave 249 passes thefocal point 250, it continues along its radial path and disburses.Multiple transducer embodiments may be oriented in any number ofconfigurations, including linear, radial, and semi-spherical arrays.

In treatments using planar ultrasonic transducers, the emitted waves donot converge at a specific point. As shown in FIG. 18C, the waves 249instead travel in a planar fashion from the edge of the transducer 252.Additionally, the ultrasound signal can be attenuated such that itterminates at a given distance and does not propagate into the deepnon-target tissue. Both planar 252 and focused 251 transducers mayinduce ultrasound hyperthermia. Used in conjunction with technology forprotecting non-target tissue (e.g., cooling system/element), asdescribed elsewhere herein, both methods of ultrasound can isolateheating to the target tissue.

Chemical Thermal Reaction

Another method for the reduction of sweat production is illustrated inFIG. 19. In the illustrated embodiment, the sweat glands are thermallydisabled by a controlled chemical reaction. This chemical reaction canbe either exothermic or endothermic and can involve one or morecomponents. The components can reside in one or more chemical reservoirs253 in communication with an interstitial probe 254. The probe 254comprises at least one lumen 255 in communication with the chemicalreservoir(s) 253, a sharp tip 256 for penetrating the skin and enteringthe target tissue and a thermally conductive element 257 comprising athermally conductive material (e.g., a metal such as copper). Thethermally conductive element portion 257 of the probe 254 is configuredto be positioned adjacent the target tissue. In one embodiment, theprobe 254 with the sharp tip 256 approaches the target tissue parallelto the skin, with a portion of the skin 177 lifted to allow the tip 256to puncture through tissue. The thermally conductive material 257 ispositioned at a location on the probe 254 to be located in the targettissue region. Further details regarding this delivery mechanism aredescribed below. The components can be delivered simultaneously orsequentially such that they mix and undergo a reaction in the thermallyconductive element 257. For an exothermic reaction, acid (e.g., HCl,H₂SO₄) and water, for example, can be delivered into the thermallyconductive element 257 in sufficient amounts to generate sufficient heatto disable and/or ablate the sweat glands via conduction across theelement 257. In another embodiment, supersaturated sodium acetate isintroduced into the thermally conductive element 257 wherein heat isgenerated as the solution crystallizes. In an alternate embodiment, thecomponents can be mixed prior to introduction into the thermallyconductive element 257. Optionally, a catalyst can be placed within thethermally conductive element 257, or elsewhere along the probe's lumen255, to facilitate the chemical reaction.

In another embodiment related to treating target tissue, a solution canbe used to carry an electric charge to treat the target tissue. In thisembodiment, an electrically conductive liquid, such as a hypertonicsolution (e.g., saline), can be injected into or around the targettissue with a syringe and needle and then electrically charged by anelectrode located proximate to the target tissue. Alternatively, theneedle itself may comprise an electrode to directly charge the solutiononce it is deposited in or adjacent to the target tissue. For example,an array of microneedles (such as that shown in FIG. 14) but alsocomprising electrodes can be used to deliver hypertonic solution to thetarget tissue, wherein the tissue is treated by the electrical chargeconducted through the solution following activation of the electrodes.

Since sweat already travels a path from the intimate regions of thesweat gland to the surface of the skin, it may be advantageous to usethe conductivity of the sweat itself to reach the sweat gland. FIGS.20A-20C illustrate a method of delivering an electrical charge to sweatglands via the sweat. To prevent injury to the skin surface andsurrounding tissue along the duct 109 of the sweat gland, it may bedesirable to first apply an insulator coating 258 to cover the skinsurface and duct 109 walls while still leaving a path for the sweat totravel from the sweat gland to the surface. Following the application ofinsulation 258, the patient can be induced to sweat by administering aninjection of epinephirine or a cholinergic agent or agonist, stimulatingthe nerves with an electrical signal, and/or increasing the patient'sbody temperature via exercise or other means. Once sweat reaches theskin's surface, the operator can apply electrical energy 259 from anenergy source (e.g., RF generator 204) to this surface sweat. Throughthe electrical conductivity of the sweat, the electrical energy 259 fromthe energy source 204 can reach and disable the sweat gland. It may bedesirable for the operator to induce sweating for the entirety of thetreatment to maintain continuity of the conductive path in someembodiments.

B. Chemical Treatment

In another embodiment for treating target tissue, a chemical treatmentsubstance can be introduced into or near the target tissue to cause achemical reaction and resulting treatment effect. For example, alcohols,acids or bases can be delivered to the target tissue to chemicallyablate the tissue. More specifically, the injection of small quantitiesof acids such as tricholoracetate or alphahydroxy acid can result in atreatment effect. Ethanol in concentrations from 5% to 100% has beenused to treat hepatocellular carcinoma, thyroid glands, fibroids andcysts in the body and can be used to treat target tissue in thisapplication. The chemical treatment substance can be delivered to thetarget tissue by any number of mechanisms, including a syringe andneedle or a microneedle patch as described elsewhere herein.

C. Mechanical Treatment Percutaneous Excision

FIGS. 21A-21C illustrate a method and device for percutaneous excisionof sweat glands. A probe 260 equipped with a retractable cutter or blade261 can be percutaneously inserted under target tissue 105 comprisingone or more sweat glands. Optionally, imaging technology can be utilizedto facilitate placement of the probe/cutter 260. The probe 260 isconfigured with a hollow chamber 262 such that the blade 261 forms theouter wall of the chamber 262. When the blade 261 is in the retractedposition, the chamber 262 is open. When the blade 261 is engaged, thechamber 262 is closed. As illustrated in FIG. 21A, the probe 260 isplaced under one or more sweat glands such that at least one sweat glandis supported by the wall of the engaged blade 261. When the blade 261 isretracted, as shown in FIG. 21B, the sweat gland drops into the openhollow chamber 262. When the blade 261 is advanced and engaged, thesweat gland is sheared from the duct 109 and falls within the probe'schamber 262. To facilitate the shearing of the gland, it may bedesirable for the blade 261 to rotate, vibrate and/or oscillate. Withthe blade 261 engaged, the sheared gland is contained within the chamber262 such that it can be removed with the probe 260 following thetreatment or vacuum aspirated coincident with the treatment.

Planar Cutting Devices

In another embodiment for treating target tissue, a planar cuttingdevice can be inserted into the target tissue via a small incision orpuncture in the skin. This device can be configured to translatelaterally, longitudinally and/or angularly within a plane of targettissue such that it shears, scrapes and/or cuts the target structureswithin the target tissue to result in a treatment effect. Morespecifically, the device can move across the interface between thedermal layer and subcutaneous layer of the skin to destroy the eccrineand apocrine glands or, at least, render them inoperable.

In one embodiment of a planar cutting device, the device can have areduced profile configuration when inserted into the skin and anexpanded profile when positioned in the target tissue. For example, asillustrated in FIGS. 22A and 22B, a device 263 comprising at least onewire 264 in a low profile configuration is inserted into an opening inthe skin. Following insertion into the skin, an actuator 265 can be usedto bow out the wire 264 into an expanded profile and cut and disabletarget structures within the target tissue during this expansion. In itsexpanded profile, the wire 264 has access to a large area of targettissue to treat. Optionally, the wire 264 can be expanded and contractedmultiple times with the actuator 265 to yield a treatment effect. Asshown in FIG. 22B, the actuator 265 may comprise an outer element 266and inner element 267. The inner element 267 comprises a shaft having adistal end 268 that is coupled to the wire 264 and a proximal end 269that extends at least partially outside of the patient. The outerelement 266 may comprise a collar or sheath that is coupled to the wire264, wherein the contraction and expansion of the wire 264 can beactuated by the movement of inner element 267 relative to the outerelement 266.

In another embodiment, as illustrated in FIG. 23, the planar cuttingdevice comprises a pinwheel cutter 270 that is positioned into thetarget tissue 105 in a reduced profile configuration. The pinwheelcutter 270 is comprised of a handle 271 for insertion into a least aportion of the target tissue 105 and at least one blade 272 that isrotatably coupled to the distal portion 273 of the handle 271. The blade272 is configured to rotate about the distal portion 273 of the handle271 such that the target tissue 105 and target structures in the blade'spath are injured and disabled.

In another embodiment relating to a planar cutting device, a guided wirecan be introduced into the target tissue and routed through the tissueto define a plane of tissue to be treated. As illustrated in FIG. 24, awire 274 is tunneled through the target tissue 105 through two insertionpoints 275 in the skin. Once the wire 274 is positioned such that itdefines an area of tissue to be treated and each end of the wire 274 ispositioned outside of the insertion points 275, tension can be appliedto both ends of the wire 274 to pull the wire 274 through the definedplane of tissue. As the wire 274 translates through the tissue, it willinjure and disable the target structures in its path. In an alternateembodiment, as shown in FIG. 25, the wire 274 is configured to beinserted into the target tissue 105, guided across the target tissue 105to define a treatment area and routed out of the body all through asingle insertion point 275 in the skin. Once the wire 274 is in placeand both ends of the wire 274 are positioned outside the insertionpoint, the wire ends can be pulled to sweep the wire 274 through thetreatment area.

In the planar cutting devices discussed above utilizing guided wires, itmay be desirable to route the wire through the target tissue to define aplane of target tissue for treatment. A tunneling instrument with asteerable tip can be used to facilitate the positioning and routing ofthe wire in and through the target tissue. A tunneling instrument 276comprising a proximal end 279 and a distal end 278 is shown in FIGS. 26Aand 26B. The instrument 276 further comprises a hollow passageway 277for routing a guided wire 274 from the proximal end 279 through thedistal end 278 for placement in the target tissue. The distal end 278 ofthe instrument 276 is configured for insertion through the skin and intothe target tissue. The proximal end 279 of the instrument is locatedoutside the body and used to facilitate the insertion and positioning ofthe distal end. This instrument 276 further comprises a steeringactuator 280 at the proximal end 279 for positioning the distal end 278of the instrument 276 and facilitating the placement of wire in thetarget tissue.

In any of the planar cutting devices discussed herein, it iscontemplated that a treatment effect can be achieved utilizing themechanical force of driving the cutting element (wire or blade as thecase may be) through the target structures within the target tissue. Itshould be understood, however, that it is also contemplated that thecutting elements of these devices may also or alternatively compriseenergy delivery elements to treat the target tissue as the element movesthrough the tissue. For example, the wire 274 in FIG. 24 could also be aresistive heating element that is connected to a power source outsidethe body, wherein the heated wire ablates and coagulates the targettissue as it translated through the planar region of treatment.Alternatively, the wire could be an energy delivery element (e.g.,electrode) for delivering one or more forms of energy (e.g.,radiofrequency, microwave, ultrasound, etc.) to the surrounding targettissue. Still alternatively, the wire and its electric field can be usedto cut and shear the target structures as it is swept through thetreatment area.

Photodynamic Glue

In another method for reducing sweating, as illustrated in FIG. 27, thesweat gland ducts 109 can be filled with photodynamic glue. In thisembodiment, a photosensitive dye 281 is introduced into the sweat ducts109 wherein the dye 281 is exposed to fluorescent light from an outsidesource. The dye 281 is preferably introduced into the eccrine and/orapocrine glands 106, 107 via topical application. With or without theassistance of pressure, the dye 281 can be applied topically for accessto the sweat ducts 109 through the pores. The dye 281 can also beintroduced into the gland or duct via injection. When exposed to lightof the necessary wavelength and for sufficient duration, the dye 281undergoes a chemical change through the cross-linking of proteins in thedye. The cross-linked dye seals the sweat duct 109 shut, therebypreventing sweat from reaching the surface of the skin.

In one embodiment, Janus green dye is delivered into the sweat duct.Optionally, pressure may be used to facilitate the delivery of dye intothe duct. Once the dye is in the duct, a laser light source from outsidethe body can deliver light of approximately 650 nanometers to the duct,thereby cross-linking the dye and sealing the duct. Rose Bengal andindocyanine green are other dyes that can be used for this application.Additionally, albumin or other proteins can be added to the dye tofacilitate the sealing action.

In another embodiment, a chromophore is mixed with a chemical agentwhereby the chemical agent and chromophore will react when exposed tofluorescent light. Specifically, the chromophore will absorb the lightand consequently heat the chemical agent, transforming the agent into aseal, thereby preventing sweat from reaching the surface of the skin.

In any of the embodiments disclosed herein relating to sealing the glandducts, such treatments can optionally include delivering energy that hasa particular affinity to water (e.g., microwave) or that is specificallyconfigured to be absorbed by water (e.g., infrared). Application ofenergy to the sweat-filled glands may result in selective treatment ofthose glands, with minimal impact to surrounding non-target tissue orstructures.

Fibrin Glue

Another method for sealing the sweat glands to reduce sweating comprisesintroducing biocompatible scaffolding into the sweat duct. Asillustrated in FIG. 28, by introducing a scaffolding structure 282 intothe sweat duct 109, fibroblast cells 283 will migrate from the skin ontothe scaffold 282 as part of the body's healing response and form scartissue that permanently seals the sweat duct 109. The scaffold 282 canbe, for example, a biodegradable fibrin hydrogel, such asglycosaminoglycen chains linked to synthetic polyamine. These scaffolds282 can be introduced into the ducts 109 from the skin surface using avariety of delivery techniques, including injection, pressure andiontophoresis.

Pressure-Induced Disablement

In another embodiment for reducing sweating, the sweat gland is disabledutilizing positive or negative pressure delivered from the skin surfaceto the sweat gland via the sweat duct. In one embodiment of thisapproach, as illustrated in FIG. 29, a piston 284 can deliverpressurized gas (e.g., air) to the sweat gland such that the pressuregradient across the sweat gland wall is sufficient to cause a disablingrupture 285 within the coils 286 of the gland. In one embodiment, apressure of at least about 200, 300, 400, 500, 600, 700 psi or more maybe used. Sufficient pressure can also be achieved by using a volumedisplacement pump, syringe or suction device.

In another embodiment, as illustrated in FIGS. 30A and 30B, the sweatglands are saturated with a liquid that has a greater volume density asa liquid than as a solid (e.g., water). The liquid may be introducedinto the sweat glands by topical application (e.g., a patch), injectionor in the case of the liquid being sweat, by inducing the patient tosweat. Cold is then applied to the liquid within the sweat gland usingany number of cryogenic techniques. As the liquid freezes, it expandsand applies pressure against the wall of the gland. The liquid continuesto freeze causing the pressure in the gland 286 to build until a rupture285 is created in the gland and/or duct 109.

Pressure-Induced Necrosis

It is believed that sweat glands may be more susceptible to ischemiathan surrounding tissue. For example, it is mentioned inPressure-Induced Bullae and Sweat Gland Necrosis Following ChemotherapyInduction, The American Journal of Medicine (Sep. 15, 2004, Volume 117),which is herein incorporated by reference in its entirety, that ischemiafrom persistent local pressure may precipitate sweat gland necrosis.Accordingly, another treatment for reducing sweat production maycomprise applying pressure to a region of target tissue at a level andfor a duration sufficient to cause necrosis in one or more sweat glandswithin the region while minimizing ischemic damage to non-target tissue,alone or in combination with other methods described herein. A device287 for causing pressure-induced necrosis in sweat glands is shown inFIG. 31. This device 287 may comprise a clamp or pincher 288 forengaging the skin at its distal end and an actuator 289 for the operatorto apply and sustain pressure. Alternatively, the actuator 289 mayfurther comprise a spring element 290 so that constant pressure can bemaintained during treatment without the need for operator assistance orintervention. The device 287 may comprise an array of clamps or pinchers288 so that multiple locations can be treated at once. In an alternativeembodiment, the device 287 could be configured for the patient to wearover a period of a few hours or a few days to achieve the desiredtreatment effect. For example, to achieve axillary anhidrosis, avariation of the device shown in FIG. 31 can be strapped to thepatient's axillae so that it can be worn overnight or over the course ofa day.

Acoustic Cavitation

In another embodiment, micro-bubbles of air are introduced into thetarget tissue and cavitated by an ultrasonic signal to achieve atreatment effect. For example, as illustrated in FIG. 32, encapsulatedmicrospheres or microbubbles 291 (e.g., OPTISON™ sold by GE Healthcare)are delivered to the target tissue 105 whereby an energy delivery devicefrom outside the body (e.g., an ultrasound transducer 292) deliversenergy 293 (e.g., an ultrasound signal) to the target tissue 105 torupture the microbubbles/microspheres 291. The microbubbles 291 can beintroduced into the glands through either topical delivery via the ducts109 or injection. The ultrasound transducer 292 can be configured todeliver a wave with an amplitude and frequency sufficient to violentlycollapse the microbubbles/microspheres 291 residing in and around thetarget structure, such that sufficient energy is released to disable thetarget structure and render a treatment effect. Alternatively,cavitation can be induced in the sweat gland by increasing the sonicpressure applied to the tissue above a threshold necessary to causenative cavitation without exogenous bubble introduction. Sodium andother ions in the sweat may act a nidus for bubble formation. Forexample, the types of pressures provided by shock wave lithotriptors maybe sufficient to generate this cavitation.

i. Protection of Non-Target Tissue

Thermal Treatment to Protect Non-Target Tissue

In thermal treatments of tissue, it may be beneficial to protect againstthe unnecessary and potentially deleterious thermal destruction ofnon-target tissue. This is particularly the case in sub-dermaltreatments since excess energy delivered to the epidermal and dermallayers of the skin can result in pain, discomfort, drying, charring andedge effects. Moreover, drying, charring and edge effects to surroundingtissue can impair a treatment's efficacy as the impedance of desiccatedtissue may be too high to allow energy to travel into deeper regions oftissue.

To avoid thermal destruction to non-target tissue and any complicationsassociated therewith, the energy delivery device can include a coolingelement for providing a cooling effect to the superficial non-targettissue (e.g., the epidermis and portions of the dermis). By conductivelyand/or convectively cooling the epidermis and allowing the coolingeffect to penetrate into the dermis, the cooling element will establisha zone of thermal protection 103 for the superficial non-target tissueas illustrated in FIG. 33. With the cooling element providing this zoneof protection 103, the target tissue (e.g., zone of thermal treatment105 in FIG. 33) can be treated with minimal risk of thermal damage tonon-target tissue.

To further reduce the risk of pain and/or other uncomfortable sensationsassociated with thermal treatment, the cooling element can further coolthe superficial non-target tissue to create a numbing effect. Dependingon the type of thermal treatment employed and the associated need forcomplementary cooling, the cooling treatment and resulting coolingand/or numbing effect may be applied before, during and/or after thethermal treatment. Protective cooling may also be applied in analternating fashion with the heating treatment to maximize energydelivery while minimizing adverse effects to non-target tissue.

The cooling element can take many forms. The cooling element can be apassive heat sink that conductively cools the skin, such as a layer ofstatic, chilled liquid (e.g., water, saline) or a solid coolant (e.g.,ice, metal plate) or some combination thereof (e.g., a metal cylinderfilled with chilled water). The cooling element can also provide activecooling in the form of a spray or stream of gas or liquid, or aerosolparticles for convective cooling of the epidermis. A thermo-electriccooler (TEC) or Peltier element can also be an effective active coolingelement. Alternatively, an active cooling element can comprise athermally conductive element with an adjacent circulating fluid to carryaway heat.

The cooling element can also be incorporated into the device as aninternal cooling component for conductively cooling non-target tissue.For example, an energy delivery device can couple a cooling component tothe energy applicator, where the cooling component can actively orpassively provide conductive cooling to adjacent tissue. When passivecooling is provided, the cooling component may comprise a cold metalplate or block. When active cooling is provided, the cooling componentmay comprise a thermally conductive element, wherein a chilled liquid(e.g., water, dry ice, alcohol, anti-freeze) is circulated through theelement's internal structure. For example, in microwave energy deliverydevices that include a dielectric, the dielectric itself can be acooling component. In another example, the cooling component can beincorporated into an electrode in embodiments where RF energy isdelivered to skin tissue.

As shown in FIG. 34A, a cooling component 115 can be incorporated intoan energy delivery device 117 comprising at least one microwave antenna120, such as described above. In this embodiment, fluid is used to cooladjacent skin tissue 119. This convective cooling can be enhanced by acoolant circulator 118 that could optionally be integrated within,coupled to or located remotely from the energy generator 113. As shownin FIG. 34B, the cooling circulator 118 is located remotely from boththe energy source 113 and energy applicator 111. The properties andcharacteristics (e.g., medium, flow rate, temperature) of thecirculating fluid (gas or liquid) can be selected and modified toachieve the desired cooling effect in light of the amount and rate ofenergy delivered to the target tissue.

A cooling element can also be used to provide a directional component toa thermal treatment. For example, the needle 294 illustrated in FIG. 35Acan be configured with a proximal region comprising a cooling element295 and a distal end comprising an electrode tip 296. In thisconfiguration, thermal damage can be isolated to the target tissue whilenon-target tissue is protectively cooled along the needle's proximalregion by the cooling element 295. Optionally, the electrode 296 itselfcan be equipped with a cooling component such that internally-circulatedchilled fluid can conductively cool tissue adjacent to the electrode296, thereby minimizing unnecessary damage to non-target tissue.

FIG. 35B shows an energy delivery element comprising a metal electrode297, an inner tube 298 and an outer circumferential surface 299. In thisembodiment, the metal electrode 297 comprises a cooling component. Anenergy generator supplies the metal electrode 297 with electrical energyto deliver an electric field to adjacent tissue. The cooling componentof the electrode 297 conductively cools the adjacent tissue, wherein acoolant is delivered to the electrode 297 through the inner tube 298 andthen circulated out through the annular space between the inner tube 298and outer circumferential surface 299.

In minimally invasive thermal treatments where the energy deliverydevice delivers energy from a position proximate or adjacent to thetarget tissue, surface cooling can be utilized in addition to or insteadof subcutaneous cooling to protect non-target tissue. For example, inFIG. 11, an energy delivery device comprising a needle 205 is depicteddelivering energy 210 subdermally. A cooling element can be incorporatedinto this delivery device to provide protective cooling adjacent to theheat treatment and/or, as illustrated, a cooling element can be appliedtopically to protect the superficial non-target tissue.

In another embodiment comprising a minimally-invasive treatment, acooling element can be incorporated into a needle such that a proximalportion and a distal portion of the needle comprise cooling elements. Inthis configuration, an electrode or other energy delivery element can besituated between the proximal and distal cooling elements such that thesuperficial non-target tissue adjacent to the proximal cooling elementand the deep non-target tissue adjacent to the distal cooling elementare protectively cooled. Accordingly, the thermal treatment is regulatedfrom above and below the treatment area such that treatment of targettissue is localized.

It may also be desirable to utilize a cooling element to improve theefficiency of the overall thermal treatment. As previously mentioned, athermal treatment may be undermined by the overheating and desiccationof tissue adjacent to the electrode or other energy delivery element.Since desiccated tissue has relatively high impedance, energy deliverybeyond the desiccated tissue is compromised, thereby resulting in aninefficient, inconsistent and potentially ineffective treatment. Byincorporating a cooling element or cooling component proximate to thetreatment site, excess heat can be absorbed by the energy deliverydevice and removed from the body. For example, an electrode or otherenergy delivery element can include a cooling component to extractexcess heat from the electrode and adjacent tissue and facilitatethermal conductivity for a deeper treatment.

In another embodiment, a heat pipe can be incorporated into the energydelivery element to absorb and expel excess energy from the treatmentarea. FIG. 36 depicts an energy delivery device 1200 comprising abipolar pair of needle-tipped electrodes 1201, 1202, wherein theelectrodes 1201, 1202 are located adjacent to target tissue 105.Incorporated within these electrodes 1201, 1202 are cooling componentscomprising heat pipes 1204, wherein the heat pipes 1204 are connected toheat sinks 1203 located outside of the body. The heat pipes 1204 operateon the principle of evaporative cooling, whereby a fluid in the pipe1204 (e.g., water, alcohol, ammonia, etc.) is rapidly condensed andevaporated at opposite ends of the pipe 1204 to transfer heat along thetube. In this example, the heat sink 1203 draws heat away from thevaporized fluid at a proximate portion of the heat pipe 1204 in order tocondense the fluid into a liquid. Once it is condensed, the liquidtravels down towards the electrode at the distal portion of the pipe andabsorbs heat from the electrode and surrounding area until it vaporizes.The vapor then travels up to the proximal portion of the heat pipe 1204to once again begin the heat exchange cycle.

In another embodiment, cooling elements can be interspersed with heatingelectrodes to achieve the desired thermal protection. For example, asshown in FIG. 37A, a cooling electrode comprising a heat sink 1205 ispositioned between two pairs 1206, 1207 of bipolar needle electrodes.The heat sink 1205 can be a thermally-conductive metal with a high heatcapacity. Optionally, the heat sink 1205 may further comprise a chamberfor holding a static or circulating cooling medium for absorbing andcarrying away excess heat. In the example illustrated in FIG. 37A, thecooling element 1205 is of a length equal to the adjacent energydelivery elements 1206, 1207 such that excess heat can be drawn awayfrom the treatment area to both protect non-target tissue and avoid theadverse consequences of desiccation of target tissue. In anotherexample, as illustrated in FIG. 37B, the cooling elements 1209 are inalternating sequence with monopolar electrodes 1208, wherein the coolingelements 1209 are shorter than the energy delivery elements 1208 so thatthey primarily provide protective cooling to the superficial non-targettissue. In any of these embodiments, the cooling elements 1209 mayalternatively comprise electrically active elements such asthermo-electric coolers (TECs) or Peltier elements.

In applications where the target tissue is thermally treated usingcryotherapy, it may be beneficial to provide a heating element toprotect non-target tissue from the undesirable effects of cooling. Asvarious modes of protective cooling have been disclosed above withrespect to heating treatments, the same conductive and convectivetechniques can analogously be employed using a heating element toprotectively heat non-target tissue in cryotherapy treatments. Inaddition to the modes of conductive and/or convective heat exchangealready disclosed, a heating element can also use resistive, radiantand/or inductive heating to provide the necessary amount of heat toprotect non-target tissue. Such protective heating treatments can beapplied before, during, after and/or in alternating sequence with theapplication of cryotherapy to treat the target tissue.

ii. Geometries

In many of the embodiments disclosed herein, treatment is administeredtopically and/or in a minimally-invasive fashion to achieve the desiredtreatment effect on target tissue. In some of these embodiments, theskin is depicted as a flat, multilayer plane of tissue, whereintreatment can be administered to target tissue in a manner that isvirtually perpendicular to its planar surface. It should be understoodthat although a treatment may be disclosed with respect to a particularskin geometry (e.g., perpendicular topical delivery, perpendicularpercutaneous insertion, etc.), such treatment may be administered withrespect any number or variety of geometries, including those discussedbelow.

Elevated Skin Treatment

In energy treatments involving the delivery of RF, infrared, microwaveor ultrasound, for example, there is the risk that the delivered energymay penetrate too deep into the body and cause harm to the deepnon-target tissue, associated critical structures (e.g., blood vessels,lymph nodes, muscle tissue, etc.) and body organs. Therefore, it may bebeneficial to elevate the target tissue comprising portion of the skinfrom the underlying tissue. Such elevation can be achieved throughmanual manipulation by the clinician or facilitated using any number ofdevices. For example, as illustrated in FIG. 38, a vacuum 147 can beused to pull and hold the skin 119, thereby elevating it for treatment.Optionally, a vacuum-suction device can be incorporated into the energydelivery device such that suction and energy delivery can be applied inunison.

In another embodiment, a tool utilizing a sterile adhesive caneffectively prop up the skin for treatment. More simply, however, aclinician can use any number of clamps, tongs or other devices toachieve and maintain skin elevation for and during treatment.

Non-Perpendicular Percutaneous Insertion

In treatments comprising minimally-invasive insertion of a treatmentdevice, it may be desirable to administer treatment by inserting thedevice into the skin tissue in a non-perpendicular fashion. Thisapproach may provide multiple benefits. First, by inserting the deviceat an angle, the risk of reaching and damaging critical structures inthe subcutaneous tissue may be minimized. For example, an angularinsertion may avoid the blood vessels, lymph nodes and muscular tissuethat lie beneath the subcutaneous tissue. Second, a non-perpendicularapproach may have a higher likelihood of achieving a planar treatment.Since the target tissue resides at a plane that's parallel to the skin'ssurface, it is believed that an angular approach can create a widertreatment per insertion.

For example, a device can be inserted into the skin at an angle and thentunneled between the dermal layer and subcutaneous layer in parallel toa region of target tissue. As shown in FIG. 39, a needle 1210 comprisingan energy delivery element can be used to deliver an energy treatment tothe target tissue in a planar fashion. In this embodiment, a needle 1210comprises an electrode, and a small portion 1211 of the needle is usedto administer multiple treatments to the parallel plane of target tissueas the needle is longitudinally retracted along its path of insertion.Alternatively, the electrode is slidably engaged with the needle 1210and treatment is administered by longitudinally translating theelectrode along the needle 1210 while the needle 1210 itself remains inplace. In another alternative embodiment, the length of the needle 1210may comprise an electrode and a segmented insulator sleeve comprising anelectrical insulator (e.g., polyimid) such that the sleeve can betranslated along the length of the electrode so that only a portion ofthe electrode is exposed at a time. Still alternatively, the needle 1210comprises multiple electrodes along its length that are dynamicallyactivated (e.g., monopolar, bipolar) simultaneously or sequentially toyield a treatment effect across the plane of target tissue.

Additionally, it may be beneficial for the operator to manipulate thepatient's skin to facilitate a non-perpendicular insertion. By pulling,holding, and/or squeezing the skin prior to, during and/or followinginsertion of the device, the operator can tunnel the device alongsidethe plane of target tissue in order to achieve a planar treatment. Thismanipulation of the skin can be performed manually by the operator or itcan be facilitated by any number of devices, including those discussedabove with respect to skin elevation. As shown in FIG. 40, a vacuumsuction 147 having multiple vacuum channels 1212 can be used to elevatethe skin 119 and facilitate the non-perpendicular insertion of one ormore energy delivery elements 120. While FIG. 40 shows six vacuumchannels 1212, it should be understood that as few as one, two, three,four, five and as many as seven, eight, nine, ten or more channels canbe used to provide suction.

In another skin geometry configuration, it may be beneficial to firstpinch and fold the patient's skin prior to delivering energy to thetarget tissue. Following the optional administration of a localanesthetic such as lidocaine (topically or subdermally), the patient'sskin can be grasped and pulled partially away such that the epidermis,dermis and subcutaneous layer are separated from the underlying skeletalmuscle. Once separated, the skin could then be folded such thatneighboring sections of the skin abut one another wherein thesubcutaneous layer of one side of the fold faces the subcutaneous layerof the other side of the fold. Isolating these adjacent subcutaneouslayers results in a treatment zone that is dense with target tissue andtarget structures. FIG. 41 shows an example of a typical skin fold 148.The skin fold 148 comprises a top 149, two sides 150 (only one visible),two edges 151 (only one visible) and a zone of “sandwiched” targettissue 152 along the longitudinal length of the fold (i.e., treatmentzone).

Focusing treatment on the target tissue rich region within the skin fold148 will allow for a more efficient procedure as two adjacent layers oftarget tissue can be treated in a single treatment. Additionally,treatment can be administered from one or more orientations (e.g., bothsides of the fold 148), which can result in a more effective andreliable treatment. Also, since the skin is being pulled away from thebody, damage to critical subcutaneous structures is minimized. Moreover,there is less risk of disruption due to thermal conductivity of bloodflow since the target tissue is further from the blood supply and theact of pinching or vacuuming the skin fold 148 into position willtemporarily cut off the blood supply to the folded tissue. Additionally,the neural activity caused in the skin by the folded configuration mayreduce the patient's pain sensation during treatment under theaforementioned gate control theory of pain management.

In one embodiment, as illustrated in FIG. 42, the skin fold 148 istreated from opposite sides by an energy delivery device 153 comprisingtwo energy delivery elements 154. The energy delivery elements 154 areconfigured to deliver energy to the treatment zone 152 in the middle ofthe fold 148. In the case of energy delivery devices 153 that compriseone or more microwave antennas connected to one or more microwavegenerators, the microwave energy can cross the outer epidermal layersfrom each side of the skin fold 148 and penetrate deep into thetreatment zone 152. To optimize the delivery of microwave energy totarget tissue, a dielectric can optionally be used in this treatment. Asshown in FIG. 42, cooling elements 115 can also be used on the skinsurface to create a zone of protection 155 for non-target tissue.Additionally, the device 153 can be configured with a cooling element115 and/or dielectric element on either side of the skin fold 148 tostabilize the fold during treatment.

Alternatively, the embodiment illustrated in FIG. 42 can achieve atreatment effect by delivering RF energy instead of microwave energy.This energy delivery device would comprise one or more electrodes oneither or both sides of the skin fold. These electrodes would eithertouch the skin surface or be in close proximity to the skin to deliveran electric field to the skin tissue. Portions of the skin tissue wouldbe resistively heated by the electric field with surrounding portionsbeing conductively heated. One or more cooling elements can be used oneither side or both sides of the skin fold to conductively and/orconvectively cool superficial non-target tissue. Alternatively, theelectrode itself can have a cooling component to provide a coolingeffect at the point of contact between the skin surface and electrode.

FIGS. 43A-43C depict three embodiments of treatment devices usingdifferent energy sources (RF, microwave and cryogenic) that areconfigured for insertion into and across the skin fold 148.Minimally-invasive insertion allows for a more localized treatment oftarget tissue such that damage to non-target tissue is minimized. Thedevices depicted in these figures may include one or more needles,micro-needles, stylets or catheters for insertion into the epidermallayer of the skin fold such that the device reaches at least a portionof the treatment zone 152. Optionally, the device can be inserted on oneside of the skin fold 148 such that the distal end of the device willexit the other side of the fold 148. The device may further comprise oneor more stabilizing plates on either side of the skin fold 148 tosupport each end of the inserted device. The stabilizing plates canoptionally comprise cooling elements to treat the epidermal tissue andcreate a zone of protected non-target tissue. Moreover, the device canbe physically or electrically connected to an energy generator forsupplying energy to be delivered to the target tissue.

FIG. 43A illustrates a minimally-invasive RF delivery device 1245including RF generator 204 comprising one or more needles 207 forinsertion into the skin fold. The needles 207 comprise one or moreelectrodes 206 strategically placed along the length of the needle 207to optimize energy delivery to and treatment of target tissue 152.Alternatively, the needle 207 itself can be an electrode. To minimizethe treatment of non-target tissue, the electrode comprising portion 206of each needle 207 can be insulated at portions 205 that will not beproximate to target tissue 152. To reduce the risk of edge effects,charring and/or desiccation at and around the point of contact betweenthe electrode 206 and tissue and resulting loss of conductivity, theneedle 207 can be coupled to one or more cooling elements or theelectrode itself can incorporate a cooling component.

The embodiment depicted in FIG. 43B comprises a minimally-invasivemicrowave delivery device 1213 comprising one or more microwave antennas120 for insertion into the skin fold 148. The antennas 120 can beinserted such that they are adjacent to the target tissue 152 tomaximize delivery of microwave energy to the sweat glands within thetreatment zone 152. To optimize the delivery of microwave energy totarget tissue over the course of the treatment, one or more antennas 120of the device 1213 may optionally be insulated with a dielectricmaterial.

The embodiment depicted in FIG. 43C comprises a minimally-invasivecryogenic therapy device 1243 including cryotherapy source reservoir1244 and one or more injection needles, stylets, cannulas or cathetersfor insertion into the skin fold 148. The stylets 211 should have one ormore passageways and openings for delivering a cryogenic fluid to thetarget tissue 152 at a rate and volume sufficient to freeze, ablateand/or disable one or more sweat glands within the target tissue 152. Aheating element may optionally be used to protect non-target tissue fromdisruptive or destructive damage. This heating element could be locatedas part of or alongside a stabilizer plate to treat the skin tissue fromthe skin surface. Alternatively or additionally, the heating elementcould be located along the interstitial portion of the device to provideprotective heating to the non-target tissue.

In the minimally-invasive treatments illustrated in FIGS. 43A-43C, theenergy delivery devices are inserted across the skin fold 148 (e.g.,transverse to the longitudinal axis of the fold). However, it should beunderstood that these devices can be configured to be inserted througheither edge and along the longitudinal length of the fold as well. Forexample, as illustrated in FIG. 44, an energy delivery device 1214 isshown inserted through an edge 151 of the skin fold 148 and positionedalong the longitudinal axis of the fold 148. As shown in FIG. 44, theneedle can optionally pierce the edge of the fold 148 opposite theinsertion point. The energy delivery device 1214 comprises a needlehaving a thermally conductive outer wall 1215 and an inner resistiveheating element 1216. A power source (e.g., battery, outlet, generator,etc.) delivers power to resistively heat the heating element and outerwall thereby thermally treating the surrounding target tissue.

FIG. 45 illustrates another approach for a minimally-invasive treatmentutilizing the skin fold configuration. In this embodiment an energydelivery element 209 is inserted through the top of the skin fold 148 sothat it is positioned in the approximate middle of the treatment zone152. This approach provides certain advantages over other approaches inthat treatment is delivered directly to the immediately surroundingtarget tissue 152 with minimal treatment to non-target tissue. As shownin FIGS. 46A and 46B, an array or rows of monopolar electrode needles207 can be used to deliver treatment along the longitudinal length ofthe skin fold. These elements can include insulation 205 at theirproximal ends to prevent unnecessary treatment of the non-target tissueat the top of the skin fold. Alternatively, a row of bipolar electrodepairs 1206, 1207 can be used to deliver treatment that will result in aconsistent planar lesion within the target tissue.

FIGS. 47A-47B show a variation of the embodiment illustrated in FIG. 45depicting a device insertion at the top of the skin fold 148. In thisembodiment, a needle 207 having a hollow passageway 1218 is firstinserted into the top of the fold 148 and through the superficialnon-target tissue 103. Once the needle 207 is in place, a bluntdissector electrode 1217 is inserted into the needle's passageway 1218and driven through the target tissue 152. When the blunt electrode 1217is placed in the treatment zone 152, it can be activated to deliver anelectric field to the treatment area to administer the thermaltreatment. Optionally, the inserted hollow needle 207 can be insulatedby a insulator 1219 (as shown in FIG. 47B) to protect non-target tissue103 from the electric field.

The use of a blunt electrode may provide certain benefits over thoseavailable using a needle electrode. First, blunt dissection tends tofollow the naturally occurring tissue plane that exists at the junctionof the dermal and subcutaneous layers, whereas one or more needleembodiments may dissect whatever tissue is in its path. Therefore, ablunt dissector can facilitate accurate electrode placement. Second, theblunt electrode's current density is more evenly distributed than thatof a needle electrode. The current density of the needle electrode isconcentrated at the needle's sharp tip such that the tissue immediatelyat the tip is heated and desiccated before a significant amount ofenergy is able to reach the surrounding tissue. Conversely, the currentdensity of a blunt electrode is evenly distributed to allow for a moreconsistent and predictable treatment.

Another embodiment utilizing the folded skin 148 configuration isdepicted in FIG. 48. In this embodiment, one or more paddle elements1221 are removably coupled (e.g., via adhesive) to each outer side ofthe skin fold 148. The paddles elements 1221 are operatively connectedto a vibration source 1222 that drives movement of the paddles 1221 inalternating sequence. Alternating movement of the paddle elements 1221,particularly between paddles on each side of the skin fold 148, createsfriction between the adjacent subcutaneous layers sandwiched within theskin fold 148. Because the sweat glands within these subcutaneous layerspossess a solid, grainy structure, the frictional contact between theabutting subcutaneous layers is high. The friction created by theopposing movement of the subcutaneous layers can mechanically deform anddamage these sweat glands and also generate frictional heat in an amountsufficient to disable or ablate at least one sweat gland within thetarget tissue. The amount of frictional heat generated will depend on anumber of factors, including, speed and power of paddle movement,frequency of paddle oscillation, the contact force between abuttingsubcutaneous layers and the adhesion force of the paddle elements 1221with the skin surface.

In another embodiment employing the skin fold geometry, treatment can beconcentrated and localized at the target tissue using focusedultrasound. As illustrated in FIG. 49, ultrasonic transducers 1223 canbe used to deliver continuous ultrasound treatment from both sides ofthe skin fold 150 using one or more channels. The energy waves from eachtransducer 1223 can be phased such that the wave from one transducer1223 can harmonize with the wave from the other transducer 1223 andyield a cumulative treatment effect at the zone of target tissue 152.The waves can also be synchronized such that they cancel one another outin areas where treatment is not desired (i.e., non-target tissue 155).Accordingly, the optimal ultrasound treatment would comprise transducersconfigured and coordinated to deliver energy waves that are additive atthe target tissue dense region but subtractive at other regions. In thisembodiment, energy waves can be delivered with frequencies from about 20kHz to 18 MHz and powers from about 0 W/cm² to 50 W/cm². Morespecifically, treatment may be most effective at frequencies from about0.5 MHz to 3 MHz and powers from about 720 mW/cm² to 50 W/cm².

Another embodiment utilizing ultrasound energy and the skin foldgeometry is shown in FIG. 50A. In this embodiment, a transducer 1223 islocated on one side 150 of the skin fold and a reflector 1224 is used onthe other side 150 of the skin fold instead of a transducer 1223. Asdiscussed above, the parameters of the remaining transducer 1223 can beset such that the propagated wave reaches its peak amplitude at thepoint it reaches the treatment zone 152 within the fold 148. In thisembodiment, the frequency of the transducer's wave and position andangle of the reflector 1224 on the opposite side of the skin fold 148can be matched to create a resonant frequency, wherein the wave that isreflected back through the skin fold by the reflector 1224 is virtuallyidentical to the initial wave. Accordingly, the treatment zone 152receives a cumulative treatment despite the use of only one transducer1223. Additionally, the use of a reflector 1224 may provide the addedbenefit of preventing ultrasound waves from straying from the treatmentsite and doing damage to non-target structures elsewhere in the body.

Many skin treatments using light energy are unable to deliver maximumenergy because the water in the blood of the skin tissue absorbs much ofthe energy. The embodiment illustrated in FIG. 50B provides a means forminimizing water absorption of delivered energy. In this embodiment,light energy 1225 is configured to be non-invasively delivered to thetreatment zone 152 and absorbed by the target tissue 152 to yield atreatment effect. In some embodiments, near infrared light is selectedat a wavelength off-peak of the highest water absorption frequency suchthat minimal light is absorbed by the blood and a significant amount ofenergy penetrates into the treatment zone. In one embodiment, the energycan be delivered at a wavelength from about 1300 to 1600 nanometers. Inanother embodiment, the energy wavelength can be from about 1400 to 1450nanometers.

In one embodiment of the approach illustrated in FIG. 50B, the lightenergy 1225 can be radiated to the skin fold 148 from one energy source.Energy penetration associated with this treatment, and the resultingtreatment effect, can be enhanced by increasing its spot size andoptical fluence. In another embodiment, the light energy 1225 can comefrom multiple sources that are focused on the treatment zone 152, suchthat the energy from multiple sources converges to the treatment zone152. In addition to near infrared, some of the various energy types thatcan be employed in this configuration include, but are not limited to,infrared and IPL. Although the embodiment shown in FIG. 50B disclosesadministering light energy 152 treatment to skin fold 148 geometry, thistreatment can also be administered using a planar geometry. One benefitof using a folded or pinched skin geometry is that some of the bloodwithin the microvasculature of the skin fold 148 will have been forcedout of the fold tissue, making the tissue more transparent to the lightenergy 1225. This benefit will be greater in the presence of vacuumpressure, as shown in FIG. 50B, since the vacuum 147 will facilitate theevacuation of blood from the skin fold.

It may be desirable to thermally protect non-target tissue inembodiments disclosed herein relating to administering thermal treatmentemploying the skin fold geometry. Thermal protection can be particularlyhelpful with this geometry because protection can be applied tonon-target tissue from either side of the skin fold as well as from thetop of the skin fold. For example, for treatments where an energydelivery device is configured to deliver thermal energy to the targettissue in the zone of treatment, cooling elements can be used at eitherside of the fold and at the top of the fold to protect non-target tissueand localize the heat treatment to the target tissue. The coolingelements can also be incorporated into the stabilizer plates on eitherside of the fold that are used to maintain the fold during treatment.

As mentioned with respect to many of the embodiment discussed above, itmay be desirable to create the skin fold with the assistance of suction.For example, a suction-vacuum cavity can be incorporated into any of theaforementioned devices. FIG. 51 shows a suction electrode 1226comprising a housing 156, a tissue chamber 157, a vacuum port (notshown) for connection to a vacuum source (not shown) and electrodes 1227connected by leads 1228 to a power source. The vacuum source can beconfigured for providing sufficient vacuum force to grasp and hold theskin in a folded orientation within the tissue chamber 157. The devicemay utilize the suction 1226 for simply grasping the skin at thebeginning of the procedure or holding the skin in place for some or allof the treatment. This area of lower pressure or suction within thedevice 1226 will help adhere the device 1226 to the skin, bringing thetarget tissue into closer apposition to the electrode antenna 1227, andreduce blood flow in the target tissue, thereby enabling more efficientheating of the tissue.

Additionally, suction may help to control pain by triggering stretch andpressure receptors in the skin, thereby blocking pain signals via thegate control theory of pain management. The gate control theory holdsthat an overabundance of nerve signals arriving at the dorsal rootganglion of the spinal cord will overwhelm the system, and mask or blockthe transmission of pain receptor signals to the brain. This mechanismof pain management is exploited by implantable electrical pain controlsunits, TENS systems, the Optilase system and others.

FIGS. 52A, 52B and 52C illustrate alternatives embodiment where a clamp1229 is used to create and hold the skin fold 148. As illustrated inFIG. 52A, a device 1230 comprising an insulated clamp 1229 andconductive metal plates 1231 is used to deliver treatment to the skinfold 148 treatment. The metal plates 1231 are electrically connected toa power source for delivering energy to the target tissue within theskin fold 148. Conductive gel can be optionally used to ensure contactand that energy is properly delivered to the target tissue.Alternatively, the embodiments depicted in FIGS. 52B and 52C show aminimally-invasive treatment wherein the skin fold 148 is maintained bystabilizer plates 1232 on either side of the fold 148 while a needle 207referenced to the stabilizer plates 1232 is inserted through the top ofthe fold 148 to deliver treatment. The stabilizer plates 1233 in theembodiment in FIG. 52C are spring-loaded with one or more springs 1234to maintain the fold during treatment. Other non-limiting examples oftissue acquisition systems, devices, and methods that can be used withembodiments described herein are disclosed, for example, at pp. 69-71 ofU.S. Provisional Application No. 61/045,937, previously incorporated byreference in its entirety.

iii. Enhancements

1. Medications

In many of the treatments disclosed herein, the target tissue is damagedto yield a treatment effect. However, non-target tissue may also beaffected in some of these treatments. Such treatments may havecomplications such as pain, inflammation, infection, and scarring, whichmay occur both during and after treatment. Therefore, it may bebeneficial to provide the patient with medications prior to, duringand/or after the treatment to minimize the incidence and impact of thesecomplications. The medications, which could be anesthetics for pain,steroids for inflammation and antibiotics for infection, can beadministered orally, topically or via local injection.

2. Imaging

For any of the embodiments disclosed herein, it may be desirable toadminister treatment with the assistance of diagnostic medical imagingtechnology. For example, high resolution imaging such as ultrasound,magnetic resonance imaging (MRI) and optical coherence tomography (OCT)can be used to locate, identify and visualize the target tissue before,during and after treatment is administered to optimize the efficacy ofthe treatment. Alternatively, imaging can be used in combination withother diagnostic techniques to identify the target tissue for treatmentor determine treatment efficacy. For example, iodine staining can beused to determine the location of where a patient is sweating followingtreatment.

3. Controlled Energy Delivery w/Physiological Feedback Loop

With some of the treatments disclosed herein for delivering energy totarget tissue, controlled delivery of energy may be helpful in avoidingunnecessary damage to target tissue (e.g., desiccation, charring, etc.)and non-target tissue as a result of overheating. A controlled deliveryof energy may also result in a more consistent, predictable andefficient overall treatment. Accordingly, it may be beneficial toincorporate into the energy delivery system a controller havingprogrammed instructions for delivering energy to tissue. Additionally,these programmed instructions may comprise an algorithm for automatingthe controlled delivery of energy.

In an embodiment employing the controlled delivery of energy, theaforementioned controller can be incorporated into or coupled to a powergenerator, wherein the controller commands the power generator inaccordance with a preset algorithm comprising temperature and/or powerprofiles. These profiles may define parameters that can be used in orderto achieve the desired treatment effect in the target tissue. Theseparameters may include, but are not limited to, power and timeincrements, maximum allowable temperature, and ramp rate (i.e., the rateof temperature/power increase). Feedback signals comprising real-time ordelayed physiological and diagnostic measurements can be used tomodulate these parameters and the overall delivery of energy. Among themeasurements that can be taken, temperature, impedance and/or reflectedpower at the treatment site and/or target tissue can be particularlyuseful. These measurements may help monitor the effect that the energydelivery has at the treatment site and at the target tissue over thecourse of the treatment. The energy controller may have fixedcoefficients or the controller coefficients may be varied depending uponthe sensed tissue response to energy delivery. Additionally, analgorithm comprising a safety profile may be employed to limit energydelivery or to limit sensed tissue temperature. These algorithms couldshut off energy delivery or modulate the energy delivery. Additionally,in treatments where thermal protection is employed, such as an activecooling element, the protective cooling can be modulated based on themonitored data.

By considering temperature measurements in the delivery of energy,treatment can be administered to achieve the necessary treatment effectwhile avoiding unnecessary complications of the treatment. For example,energy delivery to target tissue can be steadily increased (i.e., rampedup) until the desired threshold temperature is reached for the targettissue, wherein the threshold temperature is that which is necessary toyield a treatment effect. By ceasing the power increase, or the deliveryof energy altogether, once the threshold temperature is reached, harm tonon-target tissue resulting from additional and excessive heating can beavoided.

Temperature can be measured using any number of sensors, includingthermocouples and thermistors, wherein such sensors can be incorporatedinto the energy delivery element, the energy delivery device and/or theenergy delivery system. For example, in an RF energy delivery system, athermocouple can be imbedded in the electrode that delivers the RFenergy, positioned adjacent to the electrode as part of the energydelivery device or located separate from the device such that thethermocouple is wired directly to the generator. The temperaturemeasured can be that of the tissue immediately adjacent the device, thetarget tissue or any other tissue that may provide useful temperaturemeasurements. In cases where the energy delivery element is in thermalcommunication with the surrounding tissue (e.g., via conduction), asensor that is incorporated into the energy delivery element may measurethe temperature of the element itself.

Impedance can be measured by observing a tissue's response to electricalstimulation. This measurement is useful because it can help assess theextent of energy delivery to and through tissue. For example, energythat is directed to tissue having high impedance may have difficultyinfiltrating deeper regions of tissue. This is particularly important inthe case of skin tissue, as the impedance of skin can change over thecourse of treatment. As tissue is heated, it loses moisture and itsconductivity drops and impedance increases. If the tissue is heateduntil it is desiccated, the resistivity of the tissue may impair energydelivery to surrounding tissue via electrical conduction. Employingimpedance measurement feedback in the energy delivery system canoptimize the delivery of energy to target tissue while avoiding adverseconsequences to target and non-target tissue.

FIG. 53 shows another embodiment relating to the controlled delivery ofenergy to target tissue. In this embodiment, an array of electrodes 1235can be configured such that they are sequentially activated as adjacentbipolar pairs (e.g., 1236, 1237). For example, the first electrode 1236is the positive pole and the second electrode 1237 in the negative polein the first activation. In the second activation, the second electrode1237 serves as the positive pole and the third electrode 1238 is thenegative pole. A treatment effect can therefore be achieved between thefirst 1236 and second 1237 electrode, the second 1237 and third 1238electrode, the third 1238 and fourth 1239 electrode and the fourth 1239and fifth 1240 electrode. Additionally, since only one electrode pair isactivated at a time, each treatment in the sequence can be customizedbased on the characteristics of the tissue being treated. For example,if the impedance between the first 1236 and second 1237 electrodes ishigher than the impedance between the second 1237and third 1238electrodes, the first treatment may be applied for a longer durationthan the second treatment. This results in a higher resolution peractivation and a more accurate overall treatment.

4. Staged Treatment

In many of the treatments disclosed in this specification, it maydesirable to perform the treatment in stages. Additionally, thetreatment can be patterned such that sections of target tissue aretreated in the initial stage while other sections are treated insubsequent stages. For example, as illustrated in FIG. 54, a patientcould have the regions marked “A” treated in a first stage and theregions marked “B” treated in a second stage. Additionally, thetreatment could be broken down into further stages and additionalregions. Optionally, treatment could be administered to the same regionsin multiple stages such that each region receives treatment multipletimes. In one embodiment, in subsequent stages the treatment to aparticular region may vary, such as with an increased or decreasedamount of energy, or with a different treatment type.

This approach has numerous potential benefits. First, a staged treatmentgives the body the opportunity to heal between treatments. This isparticularly important since treating or thermally damaging discreteregions of tissue over several sessions will likely have fewer and lesssevere complications compared to treating or thermally damaging arelatively large area of tissue in one session. Secondly, a patternedtreatment having small regions of treatment will elicit a more favorablehealing response. Since healing time is related to the distance thatfibroblasts must migrate from surrounding tissue, smaller treatmentareas heal much faster than larger treatment areas. FIGS. 55A-Eillustrate examples of various patterned treatments.

For the medical practitioner, a staged and patterned treatment willprovide the opportunity to track the treatment's efficacy and providefollow-up treatments tailored to the patient's specific needs. Forexample, in the case of treatments for axillary hyperhidrosis, theclinician can have follow-up sessions where sweating is mapped (e.g.,iodine staining) to (1) identify the remaining areas for treatment and(2) determine the overall reduction in sweating in the underarm area.For patients who do not necessarily desire 100% anhidrosis, a stagedtreatment may allow them to discontinue treatment at a particular point.For example, a patient suffering from a severe case of axillaryhyperhidrosis may be satisfied with a 70% reduction in sweating and mayonly wish to participate in the number of treatments necessary for suchreduction.

Additionally, a staged and patterned treatment can minimize the body'scontracture response during the healing process. In a process calledfibrosis (or scarring), fibroblasts lay down a mesh of collagen tofacilitate the healing of tissue. As the density of the scar increases,the treated area contracts, thereby tightening the skin within thatregion. In the case of treatments for axillary hyperhidrosis,contracture could potentially impair the patient's full range of armmotion. A treatment can be patterned and staged to minimize contractureand/or its impact on the patient. For example, the slender treatmentareas depicted in FIG. 55C would result in minimal axillary contractureand resulting impairment to range of arm motion.

A template can be used to facilitate the application of a staged and/orpatterned treatment. FIG. 56 illustrates a staged treatment seriescomprising three templates 158, 159, 160, wherein each template isconfigured to allow treatment to a different portion of the overalltreatment area. The template may be configured to engage the energydelivery device or one or more energy delivery elements to facilitatethe application of a staged and/or patterned treatment. The template canbe comprised of a single frame made from a wood, plastic or metal withremovable or adjustable pieces to reflect the desired pattern and/orstage. Alternatively, the template can also be a pattern that is drawnon the patient's skin using a temporary marker, tattoo or dye (e.g.,henna) that will remain over the course of multiple staged treatments.

In another embodiment, as illustrated in FIG. 57, the template patterncan be represented by different chromophores 1246, 1247, 1248corresponding to different stages of the treatment. For example,different chromophores 1246, 1247, 1248 can be injected into thepatient's skin prior to any treatment such that each chromophore 1246,1247, 1248 and the regions colored by such chromophore 1241 correspondsto one treatment stage. Once all regions have been appropriatelycolored, laser treatment can commence. At each stage of treatment, thetreatment area is irradiated with a different laser, wherein thewavelength of each laser is specifically matched to the absorptioncharacteristics of a different chromophore region.

In another application employing the color-coordinated templatedescribed above, the energy delivery device, energy applicator or energydelivery element may comprise this template. For example, in the intactmicroneedle configuration illustrated in FIG. 16, a patch ofchromophore-tipped microneedles 239 can be configured with selectivecoloring in accordance with the above color-coordinated template. Thesame patch can be used at each treatment stage, wherein differenttreatments are administered by irradiating the patch with lasers ofdifferent wavelengths.

5. Diagnosis

Embodiments of the present invention also include methods andapparatuses for identifying and diagnosing patients with hyperhidrosis.Such diagnosis can be made based on subjective patient data (e.g.,patient responses to questions regarding observed sweating) or objectivetesting. In one embodiment of objective testing, an iodine solution canbe applied to the patient to identify where on a skin surface a patientis sweating and not sweating. For example, U.S. Pat. No. 4,190,056 toTapper et al., which is hereby incorporated herein by reference in itsentirety, describes methods and means for recording sweat glandactivity. Moreover, particular patients can be diagnosed based onexcessive sweating in different parts of the body in order tospecifically identify which areas to be treated. Accordingly, thetreatment may be applied only selectively to different parts of the bodyrequiring treatment, including, for example, selectively in the hands,armpits, feet and/or face.

6. Quantifying Treatment Success

Following completion of any of the treatments described above, or anystage of a treatment, the success can be evaluated qualitatively by thepatient, or may be evaluated quantitatively by any number of ways. Forexample, a measurement can be taken of the number of sweat glandsdisabled or destroyed per surface area treated. Such evaluation could beperformed by imaging the treated area or by determining the amount oftreatment administered to the treated area (e.g., the quantity of energydelivered, the measured temperature of the target tissue, etc.). Theaforementioned iodine solution test may also be employed to determinethe extent of treatment effect. In addition, a treatment can beinitiated or modified such that the amount of sweating experienced by apatient may be reduced by a desired percentage as compared topre-treatment under defined testing criteria. For example, for a patientdiagnosed with a particularly severe case of hyperhidrosis, the amountof sweating may be reduced by about 10%, 20%, 30%, 40%, 50%, 60%, 70%,80%, 90% or more. For a patient diagnosed with a less severe or morenormal sweating profile, a step-wise reduction of sweating may beachieved, but with less resolution. For example, such a patient may onlybe able to achieve partial anhidrosis in 25% increments.

Overview of Certain Methods, Systems and Other Embodiments

In one embodiment, the present application provides a method related totreating a patient comprising identifying a patient having a conditionof excessive sweating, wherein the patient desires that sweating bereduced on at least a portion of the patient's body; positioning anenergy delivery device proximate to a skin tissue of the patient; anddelivering energy to a sweat gland of the patient sufficient to halt thesecretion of sweat by at least partially disabling or destroying thesweat gland.

In one embodiment, positioning an energy delivery device may furthercomprise positioning proximate to the skin tissue of the patient anenergy delivery element selected from the group consisting of anelectrode, antenna, ultrasound transducer, laser, light emitting diode,light bulb cryogenic probe and combinations thereof. In one embodiment,delivering energy to a sweat gland of the patient may further comprisedelivering energy to the sweat gland selected from the group consistingof electromagnetic, x-ray, radiofrequency, microwave, ultrasound, nearinfrared, infrared, intense pulsed light, visible light and laser andcombinations thereof. Delivering energy to a sweat gland of the patientmay further comprise heating the sweat gland, wherein heating the sweatgland may further comprise at least partially ablating the sweat gland.

In one embodiment, positioning an energy delivery device may furthercomprise inserting the energy delivery device within the skin tissue. Inone embodiment, inserting the energy delivery device within the skintissue may further comprise inserting the energy delivery device intothe skin tissue to a depth ranging from about 1 mm to about 8 mm beneaththe surface of the skin. Inserting the energy delivery device within theskin tissue may further comprise inserting in the skin tissue aninterstitial device selected from the group consisting of needles,stylets, catheters, probes and microneedles.

In one embodiment, the method may further comprise providing protectivecooling to the skin tissue. Providing protective cooling to the skintissue may further comprise positioning a cooling element proximate theskin tissue.

In one embodiment, the method may further comprise administering to thepatient a medication selected from the group consisting of anesthetics,steroids, and antibiotics. Administering medication to the patient mayfurther comprise administering the medication orally, topically or viainjection.

In one embodiment, the method may further comprise visualizing the sweatgland using medical diagnostic imaging.

In one embodiment, the method may further comprise monitoring adiagnostic parameter of the skin tissue. The diagnostic parameter may beselected from the group consisting of impedance, temperature, reflectedlight and reflected power.

In one embodiment, delivering energy to a sweat gland of the patient mayfurther comprise modulating energy delivery in response to a monitoreddiagnostic parameter.

In one embodiment, the method may further comprise quantifying thereduction of sweating achieved in the patient or the treated portion ofthe patient's body.

In accordance with the method, a patient may desire that sweat bereduced on at least a portion of the patient's body including at least aportion of the patient's axillae.

In one embodiment, the method may further comprise elevating the skintissue away from the underlying tissue prior to delivering energy to thesweat gland.

In one embodiment, provided is a method related to treating a patientfor a condition of hyperhidrosis comprising identifying an area of skintissue on a patient comprising a layer of sweat glands, wherein the areaof skin tissue produces excessive sweat relating to the hyperhidrosis;grasping the area of skin tissue to form a skin fold comprising a firstside and a second side, wherein the layer of sweat glands correspondingto the first side is adjacent to the layer of sweat glands correspondingto the second side such that the layers comprise a treatment zone; anddelivering energy to the treatment zone to yield a treatment effect,said treatment effect reducing the amount of sweating from the area ofskin tissue.

In one embodiment, the method may further comprise applying protectivecooling to at least a portion of the area of skin tissue.

In one embodiment, applying protecting cooling to at least a portion ofthe area of skin tissue may further comprise positioning a coolingelement proximate the skin fold. Positioning a cooling element proximatethe skin fold may further comprise positioning a first cooling elementproximate the first side of the skin fold and a second cooling elementproximate the second side of the skin fold.

In one embodiment, grasping the area of skin tissue to form a skin foldmay further comprise providing suction to the area of skin tissue.Providing suction to the area of skin tissue may further comprisemaintaining suction to the area of skin tissue during the treatment.

In one embodiment, provided is a method related to reducing sweating ina patient comprising elevating a skin tissue of the patient, wherein theskin tissue comprises a target tissue comprising at least one sweatgland; and delivering energy to the target tissue, said delivery ofenergy at least partially disabling or destroying the at least one sweatgland to reduce sweating from the skin tissue of the patient.

In one embodiment, delivering energy to the target tissue may furthercomprise positioning an energy delivery device proximate to the skintissue of the patient. In one embodiment, positioning an energy deliverydevice may further comprise positioning proximate to the skin tissue ofthe patient an energy delivery element selected from the groupconsisting of an electrode, antenna, ultrasound transducer, laser, lightemitting diode, light bulb cryogenic probe and combinations thereof. Inanother embodiment, positioning an energy delivery device may furthercomprise inserting the energy delivery device within the skin tissue.Inserting the energy delivery device within the skin tissue may furthercomprise positioning an insertion element energy delivery elementproximate to the target tissue.

In one embodiment, the energy delivery element may be selected from thegroup consisting of an electrode, antenna, ultrasound transducer, laser,light emitting diode, light bulb and combinations thereof.

In one embodiment, elevating the skin tissue may further compriseapplying suction to the skin tissue.

In one embodiment, the method may further comprise providing protectivecooling to the skin tissue. Providing protective cooling to the skintissue may further comprise positioning a cooling element proximate theskin tissue.

In one embodiment, delivering energy to the target tissue may furthercomprise delivering energy to a first portion of the target tissue at afirst time and delivering energy to a second portion of the targettissue at a second time. The first time and second time may be separatedby a predetermined period of time. The predetermined period of time maybe selected from the group consisting of 1-7 days, 1-4 weeks, and 1-4months.

In one embodiment, provided is an apparatus related to treating a sweatgland of a patient comprising an energy generator and an energy deliverydevice configured for placement proximate a skin tissue of the patient,wherein the energy delivery device is coupled to the energy generator,and wherein the energy delivery device is configured to deliver energyto a target tissue within the skin tissue sufficient to at leastpartially destroy or disable at least one sweat gland within the targettissue.

In some embodiments, the energy delivery device may be configured forinsertion into the target tissue.

In some embodiments, the energy delivery device may comprise at leastone energy delivery element selected from the group consisting ofelectrodes, antennas, ultrasound transducers, lasers, light emittingdiodes, light bulbs, cryogenic probes, and combinations thereof.

In one embodiment, the first apparatus may further comprise a coolingelement configured for placement proximate a non-target tissue of thepatient.

In one embodiment, the first apparatus may further comprise a suctiondevice configured for placement proximate the skin tissue of thepatient.

In one embodiment, the present application provides a second apparatusrelated to treating a target tissue of a patient comprising aninterstitial device comprising at least one needle configured forinsertion proximate to the target tissue of the patient and a lightenergy source configured for transmitting light energy to theinterstitial device, wherein the needle is configured for receiving thelight energy transmitted by the light energy source.

In one embodiment, the chromophore may generate thermal energy from thelight energy absorbed from the light energy source. The chromophore maygenerate thermal energy from the light energy absorbed from the lightenergy source. The thermal energy from the chromophore may cause atreatment effect to the target tissue. In one embodiment, the treatmenteffect to the target tissue may comprise heating the target tissue. Inanother embodiment, the treatment effect to the target tissue mayfurther comprise at least partially ablating the target tissue. In yetanother embodiment, the treatment effect to the target tissue mayfurther comprise at least partially disabling at least one targetstructure selected from the group consisting of sweat glands, hairfollicles, sebaceous glands, collagen and fat.

In some embodiments, the interstitial device may further comprise amicroneedle patch having an optically neutral backing.

Unless the context clearly requires otherwise, throughout thedescription and the claims, the words “comprise,” “comprising,” and thelike are to be construed in an inclusive sense as opposed to anexclusive or exhaustive sense; that is to say, in a sense of “including,but not limited to.” Words using the singular or plural number alsoinclude the plural or singular number respectively. When the claims usethe word “or” in reference to a list of two or more items, that wordcovers all of the following interpretations of the word: any of theitems in the list, all of the items in the list, and any combination ofthe items in the list.

The above detailed descriptions of embodiments of the invention are notintended to be exhaustive or to limit the invention to the precise formdisclosed above. Although specific embodiments of, and examples for, theinvention are described above for illustrative purposes, variousequivalent modifications are possible within the scope of the invention,as those skilled in the relevant art will recognize. For example, whilesteps are presented in a given order, alternative embodiments mayperform steps in a different order.

The various embodiments described herein can also be combined to providefurther embodiments. Related methods, apparatuses and systems utilizingmicrowave and other types of therapy, including other forms ofelectromagnetic radiation, and further details on treatments that may bemade with such therapies, are described in the above-referencedprovisional applications to which this application claims priority, theentireties of each of which are hereby incorporated by reference: U.S.Provisional Patent Application No. 60/912,889, entitled “Methods andApparatus for Reducing Sweat Production,” filed Apr. 19, 2007, U.S.Provisional Patent Application No. 61/013,274, entitled “Methods,Delivery and Systems for Non-Invasive Delivery of Microwave Therapy,”filed Dec. 12, 2007, and U.S. Provisional Patent Application No.61/045,937, entitled “Systems and Methods for Creating an Effect UsingMicrowave Energy in Specified Tissue,” filed Apr. 17, 2008. While theabove-listed applications may have been incorporated by reference forparticular subject matter as described earlier in this application,Applicants intend the entire disclosures of the above-identifiedapplications to be incorporated by reference into the presentapplication, in that any and all of the disclosures in theseincorporated by reference applications may be combined and incorporatedwith the embodiments described in the present application.

In general, the terms used in the following claims should not beconstrued to limit the invention to the specific embodiments disclosedin the specification, unless the above detailed description explicitlydefines such terms. While certain aspects of the invention are presentedbelow in certain claim forms, the inventors contemplate the variousaspects of the invention in any number of claim forms. Accordingly, theinventors reserve the right to add additional claims after filing theapplication to pursue such additional claim forms for other aspects ofthe invention.

Additional References for Incorporation

The following references describe methods, devices and other embodimentsthat may be incorporated into or used in combination with theembodiments described in this application. Each of these references isincorporated by reference herein in their entirety:

-   -   Pressure-Induced Bullae and Sweat Gland Necrosis Following        Chemotherapy Induction, The American Journal of Medicine (Sep.        15, 2004, Volume 117).    -   U.S. Pat. No. 5,190,518 to Takasu titled Surgical Device for the        Treatment of Hyper Hidrosis.    -   U.S. Pat. No. 4,190,056 to Tapper et al. titled Method and Means        for Recording Sweat Gland Activity.    -   U.S. Pat. No. 6,050,990 to Tankovich et al. titled Methods and        Devices for Inhibiting Hair Growth and Related Skin Treatments.    -   A comparative study of the surgical treatment of axillary        osmidrosis by instrument, manual and combined subcutaneous        shaving procedures, Park et al., Annals of Plastic Surgery,        Volume 41, November 1998, pg. 488-497.    -   Electrosurgery Using Insulated Needles: Treatment of Axillary        Bromhidrosis and Hyperhidrosis by Kobayashi, Journal of        Dermatological Surgery and Oncology, July 1988, pg. 749-752.    -   Selective sweat gland removal with minimal skin excision in the        treatment of axillary hyperhidrosis: a retrospective clinical        and histological review of 15 patients by Lawrence et al.,        British Journal of Dermatology, 2006, pg. 115-118.    -   U.S. Patent Application Publication No. US 2006/0111744 to Makin        et al. titled Method and System for Treatment of Sweat Glands.    -   U.S. Patent Application Publication No. US 2003/0158566 to Brett        titled Percutaneous Cellulite Removal System.

We claim:
 1. An apparatus for treating an area of skin tissue of apatient, said apparatus comprising: a microwave generator; a graspingmechanism configured to grasp the area of skin tissue to form a skinfold having a first side and a second side; a cooling element configuredto apply protective cooling to at least a portion of the area of skintissue; and first and second microwave antennas coupled to the microwavegenerator and associated with the grasping mechanism such that, when theskin fold is formed, the first microwave antenna is positioned on thefirst side of the skin fold and the second microwave antenna ispositioned on the second side of the skin fold, wherein the first andsecond microwave antennas are configured to deliver microwave energythrough the cooling element to the area of skin tissue.
 2. The apparatusof claim 1, wherein the cooling element adapted to be positionedproximate to the skin fold when skin tissue is positioned in thegrasping mechanism.
 3. The apparatus of claim 1, wherein the coolingelement comprises a first cooling element adapted to be positionedproximate the first side of the skin fold and a second cooling elementadapted to be positioned proximate to the second side of the skin foldwhen skin tissue is positioned in the grasping mechanism.
 4. Theapparatus of claim 1, wherein the grasping mechanism comprises a suctionmechanism configured to provide suction to the skin tissue when the skintissue is positioned in the grasping mechanism.
 5. The apparatus ofclaim 4, wherein the suction mechanism is configured to provide suctionto the skin tissue to position the skin tissue in the graspingmechanism.
 6. A method of treating a patient comprising: identifying anarea of skin tissue; grasping the area of skin tissue to form a skinfold, the skin fold comprising a first side and a second side, wherein,when folded, the first side is proximally adjacent to second side suchthat the layers comprise a treatment zone; applying protective coolingwith a cooling element to at least a portion of the area of skin tissue;and positioning microwave antennas on the first and second sides of theskin fold and delivering microwave energy with the microwave antennasthrough the cooling element to the treatment zone to yield a treatmenteffect, said treatment effect reducing the amount of sweating from thearea of skin tissue.
 7. The method of claim 6, wherein applyingprotective cooling to at least a portion of the area of skin tissuefurther comprises positioning the cooling element proximate the skinfold.
 8. The method of claim 7, wherein positioning the cooling elementproximate the skin fold further comprises positioning a first coolingelement proximate the first side of the skin fold and a second coolingelement proximate the second side of the skin fold.
 9. The method ofclaim 6, wherein grasping the area of skin tissue to form the skin foldfurther comprises providing suction to the area of skin tissue.
 10. Themethod of claim 9, wherein providing suction to the area of skin tissuefurther comprises maintaining suction to the area of skin tissue duringthe treatment.